Comprehensive genomic profiling reveals inactivating SMARCA4 mutations and low tumor mutational burden in small cell carcinoma of the ovary, hypercalcemic-type

Gynecologic Oncology
Douglas I LinJulia A Elvin

Abstract

Small cell carcinoma of the ovary, hypercalcemic-type (SCCOHT) is a rare, extremely aggressive neoplasm that usually occurs in young women and is characterized by deleterious germline or somatic SMARCA4 mutations. We performed comprehensive genomic profiling (CGP) to potentially identify additional clinically and pathophysiologically relevant genomic alterations in SCCOHT. CGP assessment of all classes of coding alterations in up to 406 genes commonly altered in cancer and intronic regions for up to 31 genes commonly rearranged in cancer was performed on 18 SCCOHT cases (16 exhibiting classic morphology and 2 cases exhibiting exclusive a large cell variant morphology). In addition, a retrospective database search for clinically advanced ovarian tumors with genomic profiles similar to SCCOHT yielded 3 additional cases originally diagnosed as non-SCCOHT. CGP revealed inactivating SMARCA4 alterations and low tumor mutational burden (TMB) (<6mutations/Mb) in 94% (15/16) of SCCOHT with classic morphology. In contrast, both (2/2) cases exhibiting only large cell variant morphology were hypermutated (TMB scores of 90 and 360mut/Mb) and were wildtype for SMARCA4. In our retrospective search, an index ovarian cancer patient harboring in...Continue Reading

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Citations

Apr 6, 2018·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Dimitrios NasioudisKevin Holcomb
Oct 28, 2019·International Journal of Molecular Sciences·Nashwa El Hadidy, Vladimir N Uversky
Jun 14, 2019·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Douglas I LinJulia A Elvin
Dec 18, 2019·Histopathology·Amir Momeni-Boroujeni, Sarah Chiang
Mar 17, 2019·Cancer Research·Tatiana ShorstovaMichael Witcher
Nov 22, 2019·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Natasha RekhtmanWilliam D Travis

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