Whole‐exome analysis of metaplastic breast carcinomas with extensive osseous differentiation

Autor:	Felipe C Geyer, Britta Weigelt, Larry Norton, Nebras Zeizafoun, Kimberly Dessources, John R. Lozada, Francisco Beca, Pier Selenica, Jorge S. Reis-Filho, Ana Paula Martins Sebastiao, Fresia Pareja, Hannah Y Wen, Edi Brogi
Rok vydání:	2020
Předmět:	0301 basic medicine Histology Somatic cell Breast Neoplasms Triple Negative Breast Neoplasms Biology Article Pathology and Forensic Medicine Loss of heterozygosity Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Exome Sequencing Biomarkers Tumor polycyclic compounds Humans Allele Gene Exome Oncostatin M Receptor beta Subunit Massive parallel sequencing Genetic heterogeneity TOR Serine-Threonine Kinases General Medicine Metaplastic Breast Carcinoma Gene Expression Regulation Neoplastic Oncogene Protein v-akt 030104 developmental biology 030220 oncology & carcinogenesis Mutation Cancer research Female Tumor Suppressor Protein p53 Signal Transduction
Zdroj:	Histopathology
ISSN:	1365-2559 0309-0167
Popis:	AIMS Metaplastic breast carcinoma (MBC) is a rare type of triple-negative breast cancer that shows vast histological and genetic heterogeneity. Osseous differentiation can be found in different subtypes of MBC. Whether MBCs with osseous differentiation are underpinned by specific genetic alterations has yet to be defined. The aim of this study was to investigate the repertoire of somatic mutations and copy number alterations (CNAs) in three MBCs with extensive osseous differentiation. METHODS AND RESULTS Tumour and normal DNA samples from three MBCs with extensive osseous differentiation were subjected to whole-exome sequencing. Somatic mutations, CNAs and mutational signatures were determined by use of a validated bioinformatics pipeline. Our analyses revealed clonal TP53 hotspot mutations associated with loss of heterozygosity of the wild-type allele coupled with mutations affecting genes related to the Wnt and/or the phosphoinositide 3-kinase-AKT-mammalian target of rapamycin pathways in all cases analysed. All cases showed a dominant mutational signature 1, with two cases showing a secondary signature 3 in addition to other features of homologous recombination DNA repair defects. The oncostatin M receptor gene, which plays a role in mesenchymal differentiation and bone formation, was found to be mutated in two MBCs with extensive osseous differentiation and in none of 35 previously published 35 MBCs. CONCLUSION Our findings suggest that MBCs with osseous differentiation have somatic mutations similar to those of other forms of MBC.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::155912b531e5c249c396f7271c69c7f9 https://doi.org/10.1111/his.14088 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.