Molecular characterization of high-grade serous ovarian cancers occurring in younger and older women.

To determine if the mutational landscapes and genomic features of homologous recombination DNA repair defects (HRD) vary between younger and older patients with high-grade serous ovarian cancer (HGSOC). Younger and older women were defined as bottom and top age quartiles, respectively. HGSOCs from 15 younger (median 49 years, range 35-53) and 15 older women (median 72 years, range 70-87) were subjected to whole-exome sequencing (WES). For validation, HGSOC WES data were obtained from The Cancer Genome Atlas (TCGA), including 38 younger (median 45 years, range 34-50) and 30 older women (median 74 years, range 68-84). Mutational profiles, BRCA1/2 status, genomic HRD features, and for TCGA cases RNA-sequencing-based HRD transcriptomic signatures were assessed. In the institutional cohort, pathogenic germline BRCA1/2 mutations were more frequent in younger (5/15) than older women (0/15, p = 0.042). No somatic BRCA1/2 mutations were identified. HGSOCs from older patients preferentially displayed aging-related mutational signatures and, in contrast to younger patients, harbored CCNE1 amplifications (3/15, 20%). In the TCGA cohort, pathogenic germline BRCA1 (younger 8/38, older 0/30, p = 0.007) but not BRCA2 mutations (young 3/38, older 4/30, p = 0.691) were more frequent in younger patients. Again, no somatic BRCA1/2 mutations were identified. HGSOCs from younger women more frequently displayed genomic features of HRD (all, p < 0.05), a significant HRD gene-signature enrichment, but less frequently CCNE1 amplification (p = 0.05). Immunoreactive CLOVAR subtypes were more common in HGSOCs from younger women, and proliferative subtypes in HGSOCs from older women (p = 0.041). HGSOC patients diagnosed at an older age less frequently harbor pathogenic BRCA1 germline mutations and genomic features of HRD than younger women. Individualized treatment options, particularly pertaining to use of PARP inhibitors, in older women may be warranted.

Filippova OT ，Selenica P ，Pareja F ，Vahdatinia M ，Zhu Y ，Pei X ，Riaz N ，Long Roche K ，Chi DS ，Abu-Rustum NR ，Ellenson LH ，Reis-Filho JS ，Zamarin D ，Weigelt B ... -  《-》

An immune-centric exploration of BRCA1 and BRCA2 germline mutation related breast and ovarian cancers.

Przybytkowski E ，Davis T ，Hosny A ，Eismann J ，Matulonis UA ，Wulf GM ，Nabavi S ... -  《BMC CANCER》

Classification of High-Grade Serous Ovarian Carcinoma by Epithelial-to-Mesenchymal Transition Signature and Homologous Recombination Repair Genes.

Sohn MH ，Kim SI ，Shin JY ，Kim HS ，Chung HH ，Kim JW ，Lee M ，Seo JS ... -  《Genes》

Homologous recombination deficiency should be tested for in patients with advanced stage high-grade serous ovarian cancer aged 70 years and over.

Pitiyarachchi O ，Ansell PJ ，Coleman RL ，Dinh MH ，Holman L ，Leath CA 3rd ，Werner T ，DiSilvestro P ，Morgan M ，Tew W ，Lee C ，Cunningham M ，Newton M ，Edraki B ，Lim P ，Barlin J ，Spirtos NM ，Tewari KS ，Edelson M ，Reid T ，Carlson J ，Friedlander M ... -  《-》

Characterisation of homologous recombination deficiency in paired primary and recurrent high-grade serous ovarian cancer.

Patel JN ，Braicu I ，Timms KM ，Solimeno C ，Tshiaba P ，Reid J ，Lanchbury JS ，Darb-Esfahani S ，Ganapathi MK ，Sehouli J ，Ganapathi RN ... -  《-》