Somatic genetic alterations in synchronous and metachronous low-grade serous tumours and high-grade carcinomas of the adnexa

Autor:	W. Glenn McCluggage, Britta Weigelt, R. Keira Cheetham, Nancy Bouvier, Raghu Chandramohan, Pier Selenica, Nidia L Claros, Rajmohan Murali, David N Brown, Robert A. Soslow, Donavan T. Cheng
Rok vydání:	2019
Předmět:	Adult 0301 basic medicine Neuroblastoma RAS viral oncogene homolog medicine.medical_specialty Histology endocrine system diseases Genital Neoplasms Female Somatic cell Biology medicine.disease_cause Article Pathology and Forensic Medicine Neoplasms Multiple Primary 03 medical and health sciences Exon 0302 clinical medicine Molecular genetics Biomarkers Tumor medicine Humans Gene Aged Aged 80 and over Massive parallel sequencing Cystadenoma Serous Neoplasms Second Primary General Medicine Middle Aged Cystadenocarcinoma Serous Serous fluid 030104 developmental biology 030220 oncology & carcinogenesis Disease Progression Cancer research Female KRAS Neoplasm Grading
Zdroj:	Histopathology. 74:638-650
ISSN:	0309-0167
Popis:	Aims Low-grade serous carcinomas (LGSCs) and their precursors serous borderline tumours (SBTs) characteristically harbour mutations in BRAF, KRAS or NRAS but rarely in TP53, whereas high-grade serous carcinomas (HGSCs) are characterised by frequent TP53 mutations but rare BRAF, KRAS or NRAS mutations. In a small subset of cases, LGSCs and/or SBTs develop into high-grade tumours, including HGSCs and poorly differentiated carcinomas (PDCs). Here, we sought to define the repertoire of somatic genetic alterations in low-grade serous tumours and synchronous or metachronous high-grade adnexal carcinomas. Methods and results DNA extracted from five SBTs/LGSCs and synchronous or metachronous HGSCs/PDCs and matched normal tissue was subjected to massively parallel sequencing targeting all exons and selected non-coding regions of 341 cancer-related genes. The low-grade and high-grade tumours from a given case were related, and shared mutations and copy number alterations. Progression from low-grade to high-grade lesions was observed, and involved the acquisition of additional mutations and/or copy number alterations, or shifts from subclonal to clonal mutations. Only two (an HGSC and a PDC) of the five high-grade tumours investigated harboured TP53 mutations, whereas NRAS and KRAS hotspot mutations were seen in two HGSCs and one HGSC, respectively. Conclusions Our results suggest that progression from SBT to HGSC may take place in a subset of cases, and that at least some of the rare HGSCs lacking TP53 mutations may be derived from a low-grade serous precursor.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6f76fc949cce14f5026f5f8651a49282 https://doi.org/10.1111/his.13796 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.