|
|
|
|
|
|
|
|
Abstract
Highlights
- •
- This study examined the entire exome of serous bordeline tumors (SBTs) of the ovary for somatic genetic mutations.
- •
- A very small number of mutations are characteristic of SBTs of the ovary.
- •
- Novel candidate genes for the pathogenesis of ovarian SBT were identified.
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.
0 comments :
Post a Comment
Your comments?
Note: Only a member of this blog may post a comment.