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Identifying Genomic Alterations in Patients With Stage IV Breast Cancer Using MammaSeq: An International Collaborative Study.
Shah, Osama Shiraz; Soran, Atilla; Sahin, Mustafa; Knapick, Beth A; Ugras, Serdar; Celik, Esin; Lucas, Peter C; Lee, Adrian V.
Afiliação
  • Shah OS; Magee-Womens Research Institute, Pittsburgh, PA; Integrative Systems Biology Program, University of Pittsburgh, Pittsburgh, PA.
  • Soran A; UPMC Department of Surgery, Pittsburgh, PA.
  • Sahin M; Department of General Surgery, Selçuk University, Konya, Turkey.
  • Knapick BA; Magee-Womens Research Institute, Pittsburgh, PA.
  • Ugras S; Department of Pathology, Selçuk University, Konya, Turkey.
  • Celik E; Department of Pathology, Selçuk University, Konya, Turkey.
  • Lucas PC; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA; UPMC Hillman Cancer Center, Pittsburgh, PA.
  • Lee AV; Magee-Womens Research Institute, Pittsburgh, PA; Women's Cancer Research Center, UPMC Hillman Cancer Center, Pittsburgh, PA; UPMC Hillman Cancer Center, Pittsburgh, PA; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA; Institute for Precisi
Clin Breast Cancer ; 21(3): 210-217, 2021 06.
Article em En | MEDLINE | ID: mdl-33191115
BACKGROUND: Identification of genomic alterations present in cancer patients may aid in cancer diagnosis, prognosis and therapeutic target discovery. In this study, we aimed to identify clinically actionable variants present in stage IV breast cancer (BC) samples. MATERIALS AND METHODS: DNA was extracted from formalin-fixed paraffin-embedded samples of BC (n = 41). DNA was sequenced using MammaSeq, a BC-specific next-generation sequencing panel targeting 79 genes and 1369 mutations. Ion Torrent Suite 4.0 was used to make variant calls on the raw data, and the resulting single nucleotide variants were annotated using the CRAVAT toolkit. Single nucleotide variations (SNVs) were filtered to remove common polymorphisms and germline variants. CNVkit was employed to identify copy number variations (CNVs). The Precision Medicine Knowledgebase (PMKB) and OncoKB Precision Oncology Database were used to associate clinical significance with the identified variants. RESULTS: A total of 41 samples from Turkish patients with BC were sequenced (read depth of 94-13,340; median of 1529). These patients were diagnosed with various BC subtypes including invasive ductal carcinoma, invasive lobular carcinoma, apocrine BC, and micropapillary BC. In total, 59 different alterations (49 SNVs and 10 CNVs) were identified. From these, 8 alterations (3 CNVs - ERBB2, FGFR1, and AR copy number gains and 5 SNVs - IDH1.R132H, TP53.E204∗, PI3KCA.E545K, PI3KCA.H1047R, and PI3KCA.R88Q) were identified to have some clinical significance by PMKB and OncoKB. Moreover, the top 5 genes with the most SNVs included PIK3CA, TP53, MAP3K1, ATM, and NCOR1. Additionally, copy number gains and losses were found in ERBB2, GRB7, IGFR1, AR, FGFR1, MYC, and IKBKB, and BRCA2, RUNX1, and RB1, respectively. CONCLUSION: We identified 59 unique alterations in 38 genes in 41 stage IV BC tissue samples using MammaSeqTM. Eight of these alterations were found to have some clinical significance by OncoKB and PKMB. This study highlights the potential use of cancer specific next-generation sequencing panels in clinic to get better insight into the patient-specific genomic alterations.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Regulação Neoplásica da Expressão Gênica / Variações do Número de Cópias de DNA / Sequenciamento de Nucleotídeos em Larga Escala Limite: Female / Humans Idioma: En Revista: Clin Breast Cancer Assunto da revista: NEOPLASIAS Ano de publicação: 2021 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Regulação Neoplásica da Expressão Gênica / Variações do Número de Cópias de DNA / Sequenciamento de Nucleotídeos em Larga Escala Limite: Female / Humans Idioma: En Revista: Clin Breast Cancer Assunto da revista: NEOPLASIAS Ano de publicação: 2021 Tipo de documento: Article País de publicação: Estados Unidos