1932

Abstract

The SWI/SNF (mating type ch/Sucrose NonFermentable) chromatin remodeling complexes interact with histones and transcription factors to modulate chromatin structure and control gene expression. These evolutionarily conserved multisubunit protein complexes are involved in regulating many biological functions, such as differentiation and cell proliferation. Genomic studies have revealed frequent mutations of genes encoding multiple subunits of the SWI/SNF complexes in a wide spectrum of cancer types, including gynecologic cancers. These SWI/SNF mutations occur at different stages of tumor development and are restricted to unique histologic types of gynecologic cancers. Thus, SWI/SNF mutations have to function in the appropriate tissue and cell context to promote gynecologic cancer initiation and progression. In this review, we summarize the current knowledge of SWI/SNF mutations in the development of gynecologic cancers to provide insights into both molecular pathogenesis and possible treatment implications for these diseases.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pathmechdis-012418-012917
2020-01-24
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/pathol/15/1/annurev-pathmechdis-012418-012917.html?itemId=/content/journals/10.1146/annurev-pathmechdis-012418-012917&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Kassabov SR, Zhang B, Persinger J, Bartholomew B 2003. SWI/SNF unwraps, slides, and rewraps the nucleosome. Mol. Cell 11:391–403
    [Google Scholar]
  2. 2. 
    Phelan ML, Sif S, Narlikar GJ, Kingston RE 1999. Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits. Mol. Cell 3:247–53
    [Google Scholar]
  3. 3. 
    Hu G, Schones DE, Cui K, Ybarra R, Northrup D et al. 2011. Regulation of nucleosome landscape and transcription factor targeting at tissue-specific enhancers by BRG1. Genome Res 21:1650–58
    [Google Scholar]
  4. 4. 
    Tolstorukov MY, Sansam CG, Lu P, Koellhoffer EC, Helming KC et al. 2013. Swi/Snf chromatin remodeling/tumor suppressor complex establishes nucleosome occupancy at target promoters. PNAS 110:10165–70
    [Google Scholar]
  5. 5. 
    You JS, De Carvalho DD, Dai C, Liu M, Pandiyan K et al. 2013. SNF5 is an essential executor of epigenetic regulation during differentiation. PLOS Genet 9:e1003459
    [Google Scholar]
  6. 6. 
    Wang W, Cote J, Xue Y, Zhou S, Khavari PA et al. 1996. Purification and biochemical heterogeneity of the mammalian SWI-SNF complex. EMBO J 15:5370–82
    [Google Scholar]
  7. 7. 
    Wu JI, Lessard J, Crabtree GR 2009. Understanding the words of chromatin regulation. Cell 136:200–6
    [Google Scholar]
  8. 8. 
    Mashtalir N, D'Avino AR, Michel BC, Luo J, Pan J et al. 2018. Modular organization and assembly of SWI/SNF family chromatin remodeling complexes. Cell 175:1272–88
    [Google Scholar]
  9. 9. 
    Alpsoy A, Dykhuizen EC. 2018. Glioma tumor suppressor candidate region gene 1 (GLTSCR1) and its paralog GLTSCR1-like form SWI/SNF chromatin remodeling subcomplexes. J. Biol. Chem. 293:3892–903
    [Google Scholar]
  10. 10. 
    Reisman DN, Sciarrotta J, Bouldin TW, Weissman BE, Funkhouser WK 2005. The expression of the SWI/SNF ATPase subunits BRG1 and BRM in normal human tissues. Appl. Immunohistochem. Mol. Morphol. 13:66–74
    [Google Scholar]
  11. 11. 
    Chandler RL, Brennan J, Schisler JC, Serber D, Patterson C, Magnuson T 2013. ARID1a–DNA interactions are required for promoter occupancy by SWI/SNF. Mol. Cell. Biol. 33:265–80
    [Google Scholar]
  12. 12. 
    Kadam S, McAlpine GS, Phelan ML, Kingston RE, Jones KA, Emerson BM 2000. Functional selectivity of recombinant mammalian SWI/SNF subunits. Genes Dev 14:2441–51
    [Google Scholar]
  13. 13. 
    Euskirchen G, Auerbach RK, Snyder M 2012. SWI/SNF chromatin-remodeling factors: multiscale analyses and diverse functions. J. Biol. Chem. 287:30897–905
    [Google Scholar]
  14. 14. 
    Reisman D, Glaros S, Thompson EA 2009. The SWI/SNF complex and cancer. Oncogene 28:1653–68
    [Google Scholar]
  15. 15. 
    Wilson BG, Roberts CW. 2011. SWI/SNF nucleosome remodellers and cancer. Nat. Rev. Cancer 11:481–92
    [Google Scholar]
  16. 16. 
    Pan J, McKenzie ZM, D'Avino AR, Mashtalir N, Lareau CA et al. 2019. The ATPase module of mammalian SWI/SNF family complexes mediates subcomplex identity and catalytic activity-independent genomic targeting. Nat. Genet. 51:618–26
    [Google Scholar]
  17. 17. 
    Michel BC, D'Avino AR, Cassel SH, Mashtalir N, McKenzie ZM et al. 2018. A non-canonical SWI/SNF complex is a synthetic lethal target in cancers driven by BAF complex perturbation. Nat. Cell Biol. 20:1410–20
    [Google Scholar]
  18. 18. 
    Bell AC, West AG, Felsenfeld G 1999. The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. Cell 98:387–96
    [Google Scholar]
  19. 19. 
    Kadoch C, Hargreaves DC, Hodges C, Elias L, Ho L et al. 2013. Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat. Genet. 45:592–601
    [Google Scholar]
  20. 20. 
    Shain AH, Pollack JR. 2013. The spectrum of SWI/SNF mutations, ubiquitous in human cancers. PLOS ONE 8:e55119
    [Google Scholar]
  21. 21. 
    Roberts CW, Leroux MM, Fleming MD, Orkin SH 2002. Highly penetrant, rapid tumorigenesis through conditional inversion of the tumor suppressor gene Snf5. . Cancer Cell 2:415–25
    [Google Scholar]
  22. 22. 
    Bultman SJ, Herschkowitz JI, Godfrey V, Gebuhr TC, Yaniv M et al. 2008. Characterization of mammary tumors from Brg1 heterozygous mice. Oncogene 27:460–68
    [Google Scholar]
  23. 23. 
    Mathur R, Alver BH, San Roman AK, Wilson BG, Wang X et al. 2017. ARID1A loss impairs enhancer-mediated gene regulation and drives colon cancer in mice. Nat. Genet. 49:296–302
    [Google Scholar]
  24. 24. 
    Han ZY, Richer W, Freneaux P, Chauvin C, Lucchesi C et al. 2016. The occurrence of intracranial rhabdoid tumours in mice depends on temporal control of Smarcb1 inactivation. Nat. Commun. 7:10421
    [Google Scholar]
  25. 25. 
    Longy M, Toulouse C, Mage P, Chauvergne J, Trojani M 1996. Familial cluster of ovarian small cell carcinoma: a new Mendelian entity?. J. Med. Genet. 33:333–35
    [Google Scholar]
  26. 26. 
    Martinez-Borges AR, Petty JK, Hurt G, Stribling JT, Press JZ, Castellino SM 2009. Familial small cell carcinoma of the ovary. Pediatr. Blood Cancer 53:1334–36
    [Google Scholar]
  27. 27. 
    Florell SR, Bruggers CS, Matlak M, Young RH, Lowichik A 1999. Ovarian small cell carcinoma of the hypercalcemic type in a 14 month old: the youngest reported case. Med. Pediatr. Oncol. 32:304–7
    [Google Scholar]
  28. 28. 
    Estel R, Hackethal A, Kalder M, Munstedt K 2011. Small cell carcinoma of the ovary of the hypercalcaemic type: an analysis of clinical and prognostic aspects of a rare disease on the basis of cases published in the literature. Arch. Gynecol. Obstet. 284:1277–82
    [Google Scholar]
  29. 29. 
    Young RH, Oliva E, Scully RE 1994. Small cell carcinoma of the ovary, hypercalcemic type. A clinicopathological analysis of 150 cases. Am. J. Surg. Pathol. 18:1102–16
    [Google Scholar]
  30. 30. 
    Dickersin GR, Kline IW, Scully RE 1982. Small cell carcinoma of the ovary with hypercalcemia: a report of eleven cases. Cancer 49:188–97
    [Google Scholar]
  31. 31. 
    Matias-Guiu X, Prat J, Young RH, Capen CC, Rosol TJ et al. 1994. Human parathyroid hormone–related protein in ovarian small cell carcinoma: an immunohistochemical study. Cancer 73:1878–81
    [Google Scholar]
  32. 32. 
    Young RH, Oliva E, Scully RE 1994. Small cell carcinoma of the ovary, hypercalcemic type: a clinicopathological analysis of 150 cases. Am. J. Surg. Pathol. 18:1102–16
    [Google Scholar]
  33. 33. 
    Estel R, Hackethal A, Kalder M, Munstedt K 2011. Small cell carcinoma of the ovary of the hypercalcaemic type: an analysis of clinical and prognostic aspects of a rare disease on the basis of cases published in the literature. Arch. Gynecol. Obstet. 284:1277–82
    [Google Scholar]
  34. 34. 
    Clement PB. 2005. Selected miscellaneous ovarian lesions: small cell carcinomas, mesothelial lesions, mesenchymal and mixed neoplasms, and non-neoplastic lesions. Mod. Pathol. 18:Suppl. 2S113–29
    [Google Scholar]
  35. 35. 
    Scully RE. 1979. Tumors of the Ovary and Maldeveloped Gonads Washington: Am. Regist. Pathol.
  36. 36. 
    McCluggage W, Oliva E, Connolly L, McBride H, Young R 2004. An immunohistochemical analysis of ovarian small cell carcinoma of hypercalcemic type. Int. J. Gynecol. Pathol. 23:330–36
    [Google Scholar]
  37. 37. 
    Ramos P, Karnezis AN, Craig DW, Sekulic A, Russell ML et al. 2014. Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4. Nat. Genet 46:427–29
    [Google Scholar]
  38. 38. 
    Kupryjanczyk J, Dansonka-Mieszkowska A, Moes-Sosnowska J, Plisiecka-Halasa J, Szafron L et al. 2013. Ovarian small cell carcinoma of hypercalcemic type—evidence of germline origin and SMARCA4 gene inactivation. A pilot study. Pol. J. Pathol. 64:238–46
    [Google Scholar]
  39. 39. 
    Witkowski L, Carrot-Zhang J, Albrecht S, Fahiminiya S, Hamel N et al. 2014. Germline and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type. Nat. Genet. 46:438–43
    [Google Scholar]
  40. 40. 
    Jelinic P, Mueller JJ, Olvera N, Dao F, Scott SN et al. 2014. Recurrent SMARCA4 mutations in small cell carcinoma of the ovary. Nat. Genet. 46:424–26
    [Google Scholar]
  41. 41. 
    Karnezis AN, Wang Y, Ramos P, Hendricks WP, Oliva E et al. 2016. Dual loss of the SWI/SNF complex ATPases SMARCA4/BRG1 and SMARCA2/BRM is highly sensitive and specific for small cell carcinoma of the ovary, hypercalcaemic type. J. Pathol. 238:389–400
    [Google Scholar]
  42. 42. 
    Jelinic P, Schlappe BA, Conlon N, Tseng J, Olvera N et al. 2016. Concomitant loss of SMARCA2 and SMARCA4 expression in small cell carcinoma of the ovary, hypercalcemic type. Mod. Pathol. 29:60–66
    [Google Scholar]
  43. 43. 
    Hoffman GR, Rahal R, Buxton F, Xiang K, McAllister G et al. 2014. Functional epigenetics approach identifies BRM/SMARCA2 as a critical synthetic lethal target in BRG1-deficient cancers. PNAS 111:3128–33
    [Google Scholar]
  44. 44. 
    Wilson BG, Helming KC, Wang X, Kim Y, Vazquez F et al. 2014. Residual complexes containing SMARCA2 (BRM) underlie the oncogenic drive of SMARCA4 (BRG1) mutation. Mol. Cell. Biol. 34:1136–44
    [Google Scholar]
  45. 45. 
    Schaefer IM, Agaimy A, Fletcher CD, Hornick JL 2017. Claudin-4 expression distinguishes SWI/SNF complex–deficient undifferentiated carcinomas from sarcomas. Mod. Pathol. 30:539–48
    [Google Scholar]
  46. 46. 
    Versteege I, Sevenet N, Lange J, Rousseau-Merck MF, Ambros P et al. 1998. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 394:203–6
    [Google Scholar]
  47. 47. 
    Foulkes WD, Clarke BA, Hasselblatt M, Majewski J, Albrecht S, McCluggage WG 2014. No small surprise—Small cell carcinoma of the ovary, hypercalcaemic type, is a malignant rhabdoid tumour. J. Pathol. 233:209–14
    [Google Scholar]
  48. 48. 
    Pearce CL, Templeman C, Rossing MA, Lee A, Near AM et al. 2012. Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case–control studies. Lancet Oncol 13:385–94
    [Google Scholar]
  49. 49. 
    Bulun SE. 2009. Endometriosis. N. Engl. J. Med. 360:268–79
    [Google Scholar]
  50. 50. 
    Sugiyama T, Kamura T, Kigawa J, Terakawa N, Kikuchi Y et al. 2000. Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy. Cancer 88:2584–89
    [Google Scholar]
  51. 51. 
    Kobel M, Kalloger SE, Huntsman DG, Santos JL, Swenerton KD et al. 2010. Differences in tumor type in low-stage versus high-stage ovarian carcinomas. Int. J. Gynecol. Pathol. 29:203–11
    [Google Scholar]
  52. 52. 
    Tang H, Liu Y, Wang X, Guan L, Chen W et al. 2018. Clear cell carcinoma of the ovary: clinicopathologic features and outcomes in a Chinese cohort. Medicine 97:e10881
    [Google Scholar]
  53. 53. 
    Park HK, Ruterbusch JJ, Cote ML 2017. Recent trends in ovarian cancer incidence and relative survival in the United States by race/ethnicity and histologic subtypes. Cancer Epidemiol. Biomark. Prev. 26:1511–18
    [Google Scholar]
  54. 54. 
    Mackay HJ, Brady MF, Oza AM, Reuss A, Pujade-Lauraine E et al. 2010. Prognostic relevance of uncommon ovarian histology in women with stage III/IV epithelial ovarian cancer. Int. J. Gynecol. Cancer 20:945–52
    [Google Scholar]
  55. 55. 
    Wang YK, Bashashati A, Anglesio MS, Cochrane DR, Grewal DS et al. 2017. Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes. Nat. Genet. 49:856–65
    [Google Scholar]
  56. 56. 
    Uekuri C, Shigetomi H, Ono S, Sasaki Y, Matsuura M, Kobayashi H 2013. Toward an understanding of the pathophysiology of clear cell carcinoma of the ovary. Oncol. Lett. 6:1163–73
    [Google Scholar]
  57. 57. 
    Jones S, Wang TL, Shih IM, Mao TL, Nakayama K et al. 2010. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science 330:228–31
    [Google Scholar]
  58. 58. 
    Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K et al. 2010. ARID1A mutations in endometriosis-associated ovarian carcinomas. N. Engl. J. Med. 363:1532–43
    [Google Scholar]
  59. 59. 
    Yamamoto S, Tsuda H, Takano M, Tamai S, Matsubara O 2012. Loss of ARID1A protein expression occurs as an early event in ovarian clear-cell carcinoma development and frequently coexists with PIK3CA mutations. Mod. Pathol. 25:615–24
    [Google Scholar]
  60. 60. 
    Ayhan A, Mao TL, Seckin T, Wu CH, Guan B et al. 2012. Loss of ARID1A expression is an early molecular event in tumor progression from ovarian endometriotic cyst to clear cell and endometrioid carcinoma. Int. J. Gynecol. Cancer 22:1310–15
    [Google Scholar]
  61. 61. 
    Chene G, Ouellet V, Rahimi K, Barres V, Provencher D, Mes-Masson AM 2015. The ARID1A pathway in ovarian clear cell and endometrioid carcinoma, contiguous endometriosis, and benign endometriosis. Int. J. Gynecol. Obstet. 130:27–30
    [Google Scholar]
  62. 62. 
    Anglesio MS, Papadopoulos N, Ayhan A, Nazeran TM, Noe M et al. 2017. Cancer-associated mutations in endometriosis without cancer. N. Engl. J. Med. 376:1835–48
    [Google Scholar]
  63. 63. 
    Samartzis EP, Samartzis N, Noske A, Fedier A, Caduff R et al. 2012. Loss of ARID1A/BAF250a-expression in endometriosis: a biomarker for risk of carcinogenic transformation?. Mod. Pathol. 25:885–92
    [Google Scholar]
  64. 64. 
    Wiegand KC, Hennessy BT, Leung S, Wang Y, Ju Z et al. 2014. A functional proteogenomic analysis of endometrioid and clear cell carcinomas using reverse phase protein array and mutation analysis: Protein expression is histotype-specific and loss of ARID1A/BAF250a is associated with AKT phosphorylation. BMC Cancer 14:120
    [Google Scholar]
  65. 65. 
    Samartzis EP, Noske A, Dedes KJ, Fink D, Imesch P 2013. ARID1A mutations and PI3K/AKT pathway alterations in endometriosis and endometriosis-associated ovarian carcinomas. Int. J. Mol. Sci. 14:18824–49
    [Google Scholar]
  66. 66. 
    Levine D, Cancer Genome Atlas Res. Netw., Getz G, Gabriel SB, Cibulskis K et al. 2013. Integrated genomic characterization of endometrial carcinoma. Nature 497:67–73
    [Google Scholar]
  67. 67. 
    McConechy MK, Ding J, Cheang MC, Wiegand K, Senz J et al. 2012. Use of mutation profiles to refine the classification of endometrial carcinomas. J. Pathol. 228:20–30
    [Google Scholar]
  68. 68. 
    Wiegand KC, Lee AF, Al-Agha OM, Chow C, Kalloger SE et al. 2011. Loss of BAF250a (ARID1A) is frequent in high-grade endometrial carcinomas. J. Pathol. 224:328–33
    [Google Scholar]
  69. 69. 
    Guan B, Mao TL, Panuganti PK, Kuhn E, Kurman RJ et al. 2011. Mutation and loss of expression of ARID1A in uterine low-grade endometrioid carcinoma. Am. J. Surg. Pathol. 35:625–32
    [Google Scholar]
  70. 70. 
    DeLair DF, Burke KA, Selenica P, Lim RS, Scott SN et al. 2017. The genetic landscape of endometrial clear cell carcinomas. J. Pathol. 243:230–41
    [Google Scholar]
  71. 71. 
    Fadare O, Renshaw IL, Liang SX 2012. Does the loss of ARID1A (BAF-250a) expression in endometrial clear cell carcinomas have any clinicopathologic significance? A pilot assessment. J. Cancer 3:129–36
    [Google Scholar]
  72. 72. 
    Mao TL, Ardighieri L, Ayhan A, Kuo KT, Wu CH et al. 2013. Loss of ARID1A expression correlates with stages of tumor progression in uterine endometrioid carcinoma. Am. J. Surg. Pathol. 37:1342–48
    [Google Scholar]
  73. 73. 
    Werner HM, Berg A, Wik E, Birkeland E, Krakstad C et al. 2013. ARID1A loss is prevalent in endometrial hyperplasia with atypia and low-grade endometrioid carcinomas. Mod. Pathol. 26:428–34
    [Google Scholar]
  74. 74. 
    Yen TT, Miyamoto T, Asaka S, Chui MH, Wang Y et al. 2018. Loss of ARID1A expression in endometrial samplings is associated with the risk of endometrial carcinoma. Gynecol. Oncol. 150:426–31
    [Google Scholar]
  75. 75. 
    Hendriks YM, Wagner A, Morreau H, Menko F, Stormorken A et al. 2004. Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance. Gastroenterology 127:17–25
    [Google Scholar]
  76. 76. 
    Meyer LA, Broaddus RR, Lu KH 2009. Endometrial cancer and Lynch syndrome: clinical and pathologic considerations. Cancer Control 16:14–22
    [Google Scholar]
  77. 77. 
    Niskakoski A, Pasanen A, Lassus H, Renkonen-Sinisalo L, Kaur S et al. 2018. Molecular changes preceding endometrial and ovarian cancer: a study of consecutive endometrial specimens from Lynch syndrome surveillance. Mod. Pathol. 31:1291–301
    [Google Scholar]
  78. 78. 
    Bosse T, ter Haar NT, Seeber LM, v Diest PJ, Hes FJ et al. 2013. Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations, TP53 and microsatellite instability in endometrial cancer. Mod. Pathol. 26:1525–35
    [Google Scholar]
  79. 79. 
    Silva EG, Deavers MT, Bodurka DC, Malpica A 2006. Association of low-grade endometrioid carcinoma of the uterus and ovary with undifferentiated carcinoma: a new type of dedifferentiated carcinoma?. Int. J. Gynecol. Pathol. 25:52–58
    [Google Scholar]
  80. 80. 
    Kuhn E, Ayhan A, Bahadirli-Talbott A, Zhao C, Shih IM 2014. Molecular characterization of undifferentiated carcinoma associated with endometrioid carcinoma. Am. J. Surg. Pathol. 38:660–65
    [Google Scholar]
  81. 81. 
    Tafe LJ, Garg K, Chew I, Tornos C, Soslow RA 2010. Endometrial and ovarian carcinomas with undifferentiated components: clinically aggressive and frequently underrecognized neoplasms. Mod. Pathol. 23:781–89
    [Google Scholar]
  82. 82. 
    Ramalingam P, Croce S, McCluggage WG 2017. Loss of expression of SMARCA4 (BRG1), SMARCA2 (BRM) and SMARCB1 (INI1) in undifferentiated carcinoma of the endometrium is not uncommon and is not always associated with rhabdoid morphology. Histopathology 70:359–66
    [Google Scholar]
  83. 83. 
    Silva EG, Deavers MT, Malpica A 2007. Undifferentiated carcinoma of the endometrium: a review. Pathology 39:134–38
    [Google Scholar]
  84. 84. 
    Espinosa I, Lee CH, D'Angelo E, Palacios J, Prat J 2017. Undifferentiated and dedifferentiated endometrial carcinomas with POLE exonuclease domain mutations have a favorable prognosis. Am. J. Surg. Pathol. 41:1121–28
    [Google Scholar]
  85. 85. 
    Stewart CJ, Crook ML. 2015. SWI/SNF complex deficiency and mismatch repair protein expression in undifferentiated and dedifferentiated endometrial carcinoma. Pathology 47:439–45
    [Google Scholar]
  86. 86. 
    Coatham M, Li X, Karnezis AN, Hoang LN, Tessier-Cloutier B et al. 2016. Concurrent ARID1A and ARID1B inactivation in endometrial and ovarian dedifferentiated carcinomas. Mod. Pathol. 29:1586–93
    [Google Scholar]
  87. 87. 
    Kobel M, Hoang LN, Tessier-Cloutier B, Meng B, Soslow RA et al. 2018. Undifferentiated endometrial carcinomas show frequent loss of core switch/sucrose nonfermentable complex proteins. Am. J. Surg. Pathol. 42:76–83
    [Google Scholar]
  88. 88. 
    Strehl JD, Wachter DL, Fiedler J, Heimerl E, Beckmann MW et al. 2015. Pattern of SMARCB1 (INI1) and SMARCA4 (BRG1) in poorly differentiated endometrioid adenocarcinoma of the uterus: analysis of a series with emphasis on a novel SMARCA4-deficient dedifferentiated rhabdoid variant. Ann. Diagn. Pathol. 19:198–202
    [Google Scholar]
  89. 89. 
    Karnezis AN, Hoang LN, Coatham M, Ravn S, Almadani N et al. 2016. Loss of switch/sucrose non-fermenting complex protein expression is associated with dedifferentiation in endometrial carcinomas. Mod. Pathol. 29:302–14
    [Google Scholar]
  90. 90. 
    Agaimy A, Bertz S, Cheng L, Hes O, Junker K et al. 2016. Loss of expression of the SWI/SNF complex is a frequent event in undifferentiated/dedifferentiated urothelial carcinoma of the urinary tract. Virchows Arch 469:321–30
    [Google Scholar]
  91. 91. 
    Agaimy A, Daum O, Markl B, Lichtmannegger I, Michal M, Hartmann A 2016. SWI/SNF complex–deficient undifferentiated/rhabdoid carcinomas of the gastrointestinal tract: a series of 13 cases highlighting mutually exclusive loss of SMARCA4 and SMARCA2 and frequent co-inactivation of SMARCB1 and SMARCA2. Am. J. Surg. Pathol. 40:544–53
    [Google Scholar]
  92. 92. 
    Agaimy A, Cheng L, Egevad L, Feyerabend B, Hes O et al. 2017. Rhabdoid and undifferentiated phenotype in renal cell carcinoma: analysis of 32 cases indicating a distinctive common pathway of dedifferentiation frequently associated with SWI/SNF complex deficiency. Am. J. Surg. Pathol. 41:253–62
    [Google Scholar]
  93. 93. 
    Helming KC, Wang X, Wilson BG, Vazquez F, Haswell JR et al. 2014. ARID1B is a specific vulnerability in ARID1A-mutant cancers. Nat. Med. 20:251–54
    [Google Scholar]
  94. 94. 
    Kolin DL, Dong F, Baltay M, Lindeman N, MacConaill L et al. 2018. SMARCA4-deficient undifferentiated uterine sarcoma (malignant rhabdoid tumor of the uterus): a clinicopathologic entity distinct from undifferentiated carcinoma. Mod. Pathol. 31:1442–56
    [Google Scholar]
  95. 95. 
    Tessier-Cloutier B, Soslow RA, Stewart CJR, Kobel M, Lee CH 2018. Frequent loss of claudin-4 expression in dedifferentiated and undifferentiated endometrial carcinomas. Histopathology 73:299–305
    [Google Scholar]
  96. 96. 
    Folpe AL, Schoolmeester JK, McCluggage WG, Sullivan LM, Castagna K et al. 2015. SMARCB1-deficient vulvar neoplasms: a clinicopathologic, immunohistochemical, and molecular genetic study of 14 cases. Am. J. Surg. Pathol. 39:836–49
    [Google Scholar]
  97. 97. 
    Yoshida A, Yoshida H, Yoshida M, Mori T, Kobayashi E et al. 2015. Myoepithelioma-like tumors of the vulvar region: a distinctive group of SMARCB1-deficient neoplasms. Am. J. Surg. Pathol. 39:1102–13
    [Google Scholar]
  98. 98. 
    Maeda D, Mao TL, Fukayama M, Nakagawa S, Yano T et al. 2010. Clinicopathological significance of loss of ARID1A immunoreactivity in ovarian clear cell carcinoma. Int. J. Mol. Sci. 11:5120–28
    [Google Scholar]
  99. 99. 
    Yamamoto S, Tsuda H, Takano M, Tamai S, Matsubara O 2012. PIK3CA mutations and loss of ARID1A protein expression are early events in the development of cystic ovarian clear cell adenocarcinoma. Virchows Arch 460:77–87
    [Google Scholar]
  100. 100. 
    Lowery WJ, Schildkraut JM, Akushevich L, Bentley R, Marks JR et al. 2012. Loss of ARID1A-associated protein expression is a frequent event in clear cell and endometrioid ovarian cancers. Int. J. Gynecol. Cancer 22:9–14
    [Google Scholar]
  101. 101. 
    Miller RE, Brough R, Bajrami I, Williamson CT, McDade S et al. 2016. Synthetic lethal targeting of ARID1A-mutant ovarian clear cell tumors with dasatinib. Mol. Cancer Ther. 15:1472–84
    [Google Scholar]
  102. 102. 
    Katagiri A, Nakayama K, Rahman MT, Rahman M, Katagiri H et al. 2012. Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma. Mod. Pathol. 25:282–88
    [Google Scholar]
  103. 103. 
    Itamochi H, Oumi N, Oishi T, Shoji T, Fujiwara H et al. 2015. Loss of ARID1A expression is associated with poor prognosis in patients with stage I/II clear cell carcinoma of the ovary. Int. J. Clin. Oncol. 20:967–73
    [Google Scholar]
  104. 104. 
    Liu G, Xu P, Fu Z, Hua X, Liu X et al. 2017. Prognostic and clinicopathological significance of ARID1A in endometrium-related gynecological cancers: a meta-analysis. J. Cell. Biochem. 118:4517–25
    [Google Scholar]
  105. 105. 
    Nazeran T, Mason M, Lee S, Gibson-Wright B, Milne K et al. 2019. Prognostic and immunological significance of ARID1A status in endometriosis-associated ovarian cancers. Mod. Pathol. 32:Suppl.82
    [Google Scholar]
  106. 106. 
    Zhang ZM, Xiao S, Sun GY, Liu YP, Zhang FH et al. 2014. The clinicopathologic significance of the loss of BAF250a (ARID1A) expression in endometrial carcinoma. Int. J. Gynecol. Cancer 24:534–40
    [Google Scholar]
  107. 107. 
    Heckl M, Schmoeckel E, Hertlein L, Rottmann M, Jeschke U, Mayr D 2018. The ARID1A, p53 and β-catenin statuses are strong prognosticators in clear cell and endometrioid carcinoma of the ovary and the endometrium. PLOS ONE 13:e0192881
    [Google Scholar]
  108. 108. 
    Shen J, Ju Z, Zhao W, Wang L, Peng Y et al. 2018. ARID1A deficiency promotes mutability and potentiates therapeutic antitumor immunity unleashed by immune checkpoint blockade. Nat. Med. 24:556–62
    [Google Scholar]
  109. 109. 
    Gorn AH, Lin HY, Yamin M, Auron PE, Flannery MR et al. 1992. Cloning, characterization, and expression of a human calcitonin receptor from an ovarian carcinoma cell line. J. Clin. Investig. 90:1726–35
    [Google Scholar]
  110. 110. 
    Otte A, Gohring G, Steinemann D, Schlegelberger B, Groos S et al. 2012. A tumor-derived population (SCCOHT-1) as cellular model for a small cell ovarian carcinoma of the hypercalcemic type. Int. J. Oncol. 41:765–75
    [Google Scholar]
  111. 111. 
    van den Berg-Bakker CA, Hagemeijer A, Franken-Postma EM, Smit VT, Kuppen PJ et al. 1993. Establishment and characterization of 7 ovarian carcinoma cell lines and one granulosa tumor cell line: growth features and cytogenetics. Int. J. Cancer 53:613–20
    [Google Scholar]
  112. 112. 
    Wang Y, Chen SY, Colborne S, Lambert G, Shin CY et al. 2018. Histone deacetylase inhibitors synergize with catalytic inhibitors of EZH2 to exhibit antitumor activity in small cell carcinoma of the ovary, hypercalcemic type. Mol. Cancer Ther. 17:2767–79
    [Google Scholar]
  113. 113. 
    Kennison JA. 1995. The Polycomb and trithorax group proteins of Drosophila: trans-regulators of homeotic gene function. Annu. Rev. Genet. 29:289–303
    [Google Scholar]
  114. 114. 
    Wilson BG, Wang X, Shen X, McKenna ES, Lemieux ME et al. 2010. Epigenetic antagonism between Polycomb and SWI/SNF complexes during oncogenic transformation. Cancer Cell 18:316–28
    [Google Scholar]
  115. 115. 
    Wang Y, Chen SY, Karnezis AN, Colborne S, Santos ND et al. 2017. The histone methyltransferase EZH2 is a therapeutic target in small cell carcinoma of the ovary, hypercalcaemic type. J. Pathol. 242:371–83
    [Google Scholar]
  116. 116. 
    Chan-Penebre E, Armstrong K, Drew A, Grassian AR, Feldman I et al. 2017. Selective killing of SMARCA2- and SMARCA4-deficient small cell carcinoma of the ovary, hypercalcemic type cells by inhibition of EZH2: in vitro and in vivo preclinical models. Mol. Cancer Ther. 16:850–60
    [Google Scholar]
  117. 117. 
    Lang JD, Hendricks WPD, Orlando KA, Yin H, Kiefer J et al. 2018. Ponatinib shows potent antitumor activity in small cell carcinoma of the ovary hypercalcemic type (SCCOHT) through multikinase inhibition. Clin. Cancer Res. 24:1932–43
    [Google Scholar]
  118. 118. 
    Riva F, Omes C, Bassani R, Nappi RE, Mazzini G et al. 2014. In-vitro culture system for mesenchymal progenitor cells derived from waste human ovarian follicular fluid. Reprod. Biomed. Online 29:457–69
    [Google Scholar]
  119. 119. 
    Kossowska-Tomaszczuk K, De Geyter C, De Geyter M, Martin I, Holzgreve W et al. 2009. The multipotency of luteinizing granulosa cells collected from mature ovarian follicles. Stem Cells 27:210–19
    [Google Scholar]
  120. 120. 
    Friedmann-Morvinski D, Bushong EA, Ke E, Soda Y, Marumoto T et al. 2012. Dedifferentiation of neurons and astrocytes by oncogenes can induce gliomas in mice. Science 338:1080–84
    [Google Scholar]
  121. 121. 
    Guan B, Wang TL, Shih IM 2011. ARID1A, a factor that promotes formation of SWI/SNF-mediated chromatin remodeling, is a tumor suppressor in gynecologic cancers. Cancer Res 71:6718–27
    [Google Scholar]
  122. 122. 
    Guan B, Gao M, Wu CH, Wang TL, Shih IM 2012. Functional analysis of in-frame indel ARID1A mutations reveals new regulatory mechanisms of its tumor suppressor functions. Neoplasia 14:986–93
    [Google Scholar]
  123. 123. 
    Suryo Rahmanto Y, Jung JG, Wu RC, Kobayashi Y, Heaphy CM et al. 2016. Inactivating ARID1A tumor suppressor enhances TERT transcription and maintains telomere length in cancer cells. J. Biol. Chem. 291:9690–99
    [Google Scholar]
  124. 124. 
    Bitler BG, Aird KM, Garipov A, Li H, Amatangelo M et al. 2015. Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers. Nat. Med. 21:231–38
    [Google Scholar]
  125. 125. 
    Lakshminarasimhan R, Andreu-Vieyra C, Lawrenson K, Duymich CE, Gayther SA et al. 2017. Down-regulation of ARID1A is sufficient to initiate neoplastic transformation along with epigenetic reprogramming in non-tumorigenic endometriotic cells. Cancer Lett 401:11–19
    [Google Scholar]
  126. 126. 
    Goldman AR, Bitler BG, Schug Z, Conejo-Garcia JR, Zhang R, Speicher DW 2016. The primary effect on the proteome of ARID1A-mutated ovarian clear cell carcinoma is downregulation of the mevalonate pathway at the post-transcriptional level. Mol. Cell. Proteom. 15:3348–60
    [Google Scholar]
  127. 127. 
    Kelso TWR, Porter DK, Amaral ML, Shokhirev MN, Benner C, Hargreaves DC 2017. Chromatin accessibility underlies synthetic lethality of SWI/SNF subunits in ARID1A-mutant cancers. eLife 6:e30506
    [Google Scholar]
  128. 128. 
    Guan B, Rahmanto YS, Wu RC, Wang Y, Wang Z et al. 2014. Roles of deletion of Arid1a, a tumor suppressor, in mouse ovarian tumorigenesis. J. Natl. Cancer Inst. 106:dju146
    [Google Scholar]
  129. 129. 
    Chandler RL, Damrauer JS, Raab JR, Schisler JC, Wilkerson MD et al. 2015. Coexistent ARID1APIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling. Nat. Commun. 6:6118
    [Google Scholar]
  130. 130. 
    Kim M, Lu F, Zhang Y 2016. Loss of HDAC-mediated repression and gain of NF-κB activation underlie cytokine induction in ARID1A- and PIK3CA-mutation-driven ovarian cancer. Cell Rep 17:275–88
    [Google Scholar]
  131. 131. 
    Lac V, Nazeran TM, Tessier-Cloutier B, Aguirre-Hernandez R, Albert A et al. 2019. Oncogenic mutations in histologically normal endometrium: the new normal?. J. Pathol. 249:173–81
    [Google Scholar]
  132. 132. 
    Hughes CS, McConechy MK, Cochrane DR, Nazeran T, Karnezis AN et al. 2016. Quantitative profiling of single formalin fixed tumour sections: proteomics for translational research. Sci. Rep. 6:34949
    [Google Scholar]
  133. 133. 
    Cochrane DR, Tessier-Cloutier B, Lawrence KM, Nazeran T, Karnezis AN et al. 2017. Clear cell and endometrioid carcinomas: Are their differences attributable to distinct cells of origin?. J. Pathol. 243:26–36
    [Google Scholar]
  134. 134. 
    Zhai Y, Kuick R, Tipton C, Wu R, Sessine M et al. 2016. Arid1a inactivation in an Apc- and Pten-defective mouse ovarian cancer model enhances epithelial differentiation and prolongs survival. J. Pathol. 238:21–30
    [Google Scholar]
  135. 135. 
    Anglesio MS, Bashashati A, Wang YK, Senz J, Ha G et al. 2015. Multifocal endometriotic lesions associated with cancer are clonal and carry a high mutation burden. J. Pathol. 236:201–9
    [Google Scholar]
  136. 136. 
    King CM, Barbara C, Prentice A, Brenton JD, Charnock-Jones DS 2016. Models of endometriosis and their utility in studying progression to ovarian clear cell carcinoma. J. Pathol. 238:185–96
    [Google Scholar]
  137. 137. 
    Greaves E, Cousins FL, Murray A, Esnal-Zufiaurre A, Fassbender A et al. 2014. A novel mouse model of endometriosis mimics human phenotype and reveals insights into the inflammatory contribution of shed endometrium. Am. J. Pathol. 184:1930–39
    [Google Scholar]
  138. 138. 
    Serber DW, Rogala A, Makarem M, Rosson GB, Simin K et al. 2012. The BRG1 chromatin remodeler protects against ovarian cysts, uterine tumors, and mammary tumors in a lineage-specific manner. PLOS ONE 7:e31346
    [Google Scholar]
  139. 139. 
    van der Zee M, Jia Y, Wang Y, Heijmans-Antonissen C, Ewing PC et al. 2013. Alterations in Wnt-β-catenin and Pten signalling play distinct roles in endometrial cancer initiation and progression. J. Pathol. 230:48–58
    [Google Scholar]
  140. 140. 
    Helming KC, Wang X, Roberts CWM 2014. Vulnerabilities of mutant SWI/SNF complexes in cancer. Cancer Cell 26:309–17
    [Google Scholar]
  141. 141. 
    Caumanns JJ, Wisman GBA, Berns K, van der Zee AGJ, de Jong S 2018. ARID1A mutant ovarian clear cell carcinoma: a clear target for synthetic lethal strategies. Biochim. Biophys. Acta Rev. Cancer 1870:176–84
    [Google Scholar]
  142. 142. 
    Bitler BG, Fatkhutdinov N, Zhang R 2015. Potential therapeutic targets in ARID1A-mutated cancers. Expert Opin. Ther. Targets 19:1419–22
    [Google Scholar]
  143. 143. 
    Samartzis EP, Gutsche K, Dedes KJ, Fink D, Stucki M, Imesch P 2014. Loss of ARID1A expression sensitizes cancer cells to PI3K- and AKT-inhibition. Oncotarget 5:5295–303
    [Google Scholar]
  144. 144. 
    Caumanns JJ, Berns K, Wisman GBA, Fehrmann RSN, Tomar T et al. 2018. Integrative kinome profiling identifies mTORC1/2 inhibition as treatment strategy in ovarian clear cell carcinoma. Clin. Cancer Res. 24:3928–40
    [Google Scholar]
  145. 145. 
    Kwan SY, Cheng X, Tsang YT, Choi JS, Kwan SY et al. 2016. Loss of ARID1A expression leads to sensitivity to ROS-inducing agent elesclomol in gynecologic cancer cells. Oncotarget 7:56933–43
    [Google Scholar]
  146. 146. 
    Ogiwara H, Takahashi K, Sasaki M, Kuroda T, Yoshida H et al. 2019. Targeting the vulnerability of glutathione metabolism in ARID1A-deficient cancers. Cancer Cell 35:177–90
    [Google Scholar]
  147. 147. 
    Shorstova T, Marques M, Su J, Johnston J, Kleinman CL et al. 2019. SWI/SNF-compromised cancers are susceptible to bromodomain inhibitors. Cancer Res 79:2761–74
    [Google Scholar]
  148. 148. 
    Jelinic P, Ricca J, Van Oudenhove E, Olvera N, Merghoub T et al. 2018. Immune-active microenvironment in small cell carcinoma of the ovary, hypercalcemic type: rationale for immune checkpoint blockade. J. Natl. Cancer Inst. 110:787–90
    [Google Scholar]
/content/journals/10.1146/annurev-pathmechdis-012418-012917
Loading
/content/journals/10.1146/annurev-pathmechdis-012418-012917
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error