Copy number alterations in stage I epithelial ovarian cancer highlight three genomic patterns associated with prognosis

A comprehensive investigation of histotype‐specific microRNA and their variants in Stage I epithelial ovarian cancers

“…Additional cases were from matched biopsies withdrawn at relapse. The demographic and clinical features (Table 1) show that the study cohort is histologically distributed and, representative of the clinical situation 5,8,27 …”

“…As genome structural rearrangements can be, at least in part, a plausible mechanism for miRNA expression alterations, we integrated miRNA and SCNA profiles to question whether the increased expression of previously identified miRNAs could be the result of structural changes in their genomic loci. To this aim, we implemented a regression‐based model to estimate the association between the CNV profiles 8 and the miRNA expression profiles. Briefly, we considered that if the over/underexpression of a miRNA is the result of a genomic event (ie, amplification/deletion) a significant and concordant association would be expected.…”

“…(iii) each subtype can be further subclassified into three genomic profiles based on the length and the extent of somatic copy number alteration. 8 Overall, these findings suggest that the biology of Stage I EOC is more complex than depicted by histopathological data, and that a more detailed knowledge of its molecular events is mandatory to improve patients' clinical outcome.…”

“…We have recently demonstrated that Stage I EOC is molecularly characterized by three different genome instability patterns (namely stable, S, unstable, U and highly unstable, HU) lagging each histological subtype. 8 As genome structural rearrangements can be, at least in part, a plausible mechanism for miRNA expression alterations, we integrated miRNA and SCNA profiles to question whether the increased expression of previously identified miRNAs could be the result of structural changes in their genomic loci. To this aim, we implemented a regression-based model to estimate the association between the CNV profiles 8 and the miRNA profiles.…”

“…On a sizable and unique cohort of Stage I EOC our group has investigated the molecular differences that characterize each subtype and its prognosis. We demonstrated that: (i) the expression profile of a subset of miRNA acts as histotype specific biomarker for clear cell and mucinous subtypes (miR‐30a‐5p/3p and miR‐192/194, respectively) 3 ; (ii) miR‐200c is an independent prognostic biomarker of survival 4 and it is part of a more complex network composed of miRNAs, coding genes and lncRNAs which together predict patients relapse better than conventional classifiers based on anatomo‐pathology 5‐7 ; (iii) each subtype can be further subclassified into three genomic profiles based on the length and the extent of somatic copy number alteration 8 . Overall, these findings suggest that the biology of Stage I EOC is more complex than depicted by histopathological data, and that a more detailed knowledge of its molecular events is mandatory to improve patients' clinical outcome.…”