[HTML][HTML] Mutational landscape of mucinous ovarian carcinoma and its neoplastic precursors
Genome medicine, 2015•Springer
Background Mucinous ovarian tumors are an unusual group of rare neoplasms with an
apparently clear progression from benign to borderline to carcinoma, yet with a controversial
cell of origin in the ovarian surface epithelium. They are thought to be molecularly distinct
from other ovarian tumors but there have been no exome-level sequencing studies
performed to date. Methods To understand the genetic etiology of mucinous ovarian tumors
and assess the presence of novel therapeutic targets or pathways, we undertook exome …
apparently clear progression from benign to borderline to carcinoma, yet with a controversial
cell of origin in the ovarian surface epithelium. They are thought to be molecularly distinct
from other ovarian tumors but there have been no exome-level sequencing studies
performed to date. Methods To understand the genetic etiology of mucinous ovarian tumors
and assess the presence of novel therapeutic targets or pathways, we undertook exome …
Background
Mucinous ovarian tumors are an unusual group of rare neoplasms with an apparently clear progression from benign to borderline to carcinoma, yet with a controversial cell of origin in the ovarian surface epithelium. They are thought to be molecularly distinct from other ovarian tumors but there have been no exome-level sequencing studies performed to date.
Methods
To understand the genetic etiology of mucinous ovarian tumors and assess the presence of novel therapeutic targets or pathways, we undertook exome sequencing of 24 tumors encompassing benign (5), borderline (8) and carcinoma (11) histologies and also assessed a validation cohort of 58 tumors for specific gene regions including exons 4–9 of TP53.
Results
The predominant mutational signature was of C>T transitions in a NpCpG context, indicative of deamination of methyl-cytosines. As well as mutations in known drivers (KRAS, BRAF and CDKN2A), we identified a high percentage of carcinomas with TP53 mutations (52 %), and recurrent mutations in RNF43, ELF3, GNAS, ERBB3 and KLF5.
Conclusions
The diversity of mutational targets suggests multiple routes to tumorigenesis in this heterogeneous group of tumors that is generally distinct from other ovarian subtypes.
Springer