Spectrum of mutations in leiomyosarcomas identified by clinical targeted next-generation sequencing.
Exp Mol Pathol
; 102(1): 156-161, 2017 02.
Article
em En
| MEDLINE
| ID: mdl-28093192
ABSTRACT
Recurrent genomic mutations in uterine and non-uterine leiomyosarcomas have not been well established. Using a next generation sequencing (NGS) panel of common cancer-associated genes, 25 leiomyosarcomas arising from multiple sites were examined to explore genetic alterations, including single nucleotide variants (SNV), small insertions/deletions (indels), and copy number alterations (CNA). Sequencing showed 86 non-synonymous, coding region somatic variants within 151 gene targets in 21 cases, with a mean of 4.1 variants per case; 4 cases had no putative mutations in the panel of genes assayed. The most frequently altered genes were TP53 (36%), ATM and ATRX (16%), and EGFR and RB1 (12%). CNA were identified in 85% of cases, with the most frequent copy number losses observed in chromosomes 10 and 13 including PTEN and RB1; the most frequent gains were seen in chromosomes 7 and 17. Our data show that deletions in canonical cancer-related genes are common in leiomyosarcomas. Further, the spectrum of gene mutations observed shows that defects in DNA repair and chromosomal maintenance are central to the biology of leiomyosarcomas, and that activating mutations observed in other common cancer types are rare in leiomyosarcomas.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Predisposição Genética para Doença
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Sequenciamento de Nucleotídeos em Larga Escala
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Leiomiossarcoma
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Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Exp Mol Pathol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos