Whole exome sequence analysis of serous borderline tumors of the ovary

Abstract

Objective Serous borderline tumor (SBT) is a unique histopathologic entity of the ovary, believed to be intermediate between benign cystadenoma and invasive low-grade serous carcinoma. While somatic mutations in the KRAS or BRAF, and rarely ERBB2, genes have been well characterized in SBTs, other genetic alterations have not been described. Toward a more comprehensive understanding of the molecular genetic architecture of SBTs, we undertook whole exome sequencing of this tumor type. Methods Following pathologic review and laser capture microdissection to enrich for tumor cells, whole exomes were prepared from DNA of two independent SBTs and subjected to massively parallel DNA sequencing. Results Both tumors contained an activating mutation of the BRAF gene. A total of 15 additional somatic mutations were identified, nine in one tumor and six in the other. Eleven were missense mutations and four were nonsense or deletion mutations. Fourteen of the 16 genes found to be mutated in this study have been reported to be mutated in other cancers. Furthermore, 12 of these genes are mutated in ovarian cancers. The FBXW7 and KIAA1462 genes are noteworthy candidates for a pathogenic role in serous borderline tumorigenesis. Conclusions These findings suggest that a very small number of somatic genetic mutations are characteristic of SBTs of the ovary, thus supporting their classification as a relatively genetically stable tumor type. The mutant genes described herein represent novel candidates for the pathogenesis of ovarian SBT.

Hereditary Risk Evaluation for Borderline Ovarian Tumors Based on Immunohistochemistry

“…Another study that examined the entire exome of serous BOTs for somatic genetic mutations showed similar results to low-grade serous carcinomas14. We should therefore consider hereditary risk, rather than somatic mutation.…”

“…A small proportion of BOT patients are known to have a somatic mutation 14. Another genetic test for BOT showed the possibility of an additional treatment based on gene sequencing results 15.…”

JCAD Promotes Progression of Nonalcoholic Steatohepatitis to Liver Cancer by Inhibiting LATS2 Kinase Activity

“…The JCAD sequence is highly conserved in vertebrates from zebrafish to human (12), which indicates that the protein may have an important biological function. JCAD has been recently thought to be a novel candidate gene for a pathogenic role in serous borderline tumorigenesis (15). To our knowledge, its participation in oncogenesis has not been explored yet, nor has the role of JCAD in hepatic pathophysiology and carcinogenesis been investigated.…”

Molecular-Biological Characteristics of Type I, Ovarian Low-Grade Serous and Mucinous Carcinomas and Prospects of Molecular-Targeted Therapy

“…The results of exome sequencing of serous borderline tumors were recently reported. In addition to the previously reported oncogenic mutations of BRAF, FBXW7, and KIAA1462, novel gene mutations were reported [15]. Research groups from Johns Hopkins University and MD Anderson Cancer Center recently reported 2 new lines of evidence supporting the type I carcinogenesis pathway.…”