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The genetic landscape of breast carcinomas with neuroendocrine differentiation.
Marchiò, Caterina; Geyer, Felipe C; Ng, Charlotte Ky; Piscuoglio, Salvatore; De Filippo, Maria R; Cupo, Marco; Schultheis, Anne M; Lim, Raymond S; Burke, Kathleen A; Guerini-Rocco, Elena; Papotti, Mauro; Norton, Larry; Sapino, Anna; Weigelt, Britta; Reis-Filho, Jorge S.
Afiliação
  • Marchiò C; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Geyer FC; Department of Medical Sciences, University of Turin, Turin, Italy.
  • Ng CK; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Piscuoglio S; Department of Pathology, Hospital Israelita Albert Einstein, Instituto Israelita de Ensino e Pesquisa, São Paulo, Brazil.
  • De Filippo MR; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Cupo M; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Schultheis AM; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Lim RS; Department of Medical Sciences, University of Turin, Turin, Italy.
  • Burke KA; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Guerini-Rocco E; Pathology Department, University Hospital, Cologne, Germany.
  • Papotti M; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Norton L; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Sapino A; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Weigelt B; Pathology Department, European Institute of Oncology, Milan, Italy.
  • Reis-Filho JS; Department of Oncology, University of Turin, Turin, Italy.
J Pathol ; 241(3): 405-419, 2017 Feb.
Article em En | MEDLINE | ID: mdl-27925203
Neuroendocrine breast carcinomas (NBCs) account for 2-5% of all invasive breast cancers, and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), and are HER2-negative and of luminal 'intrinsic' subtype. Here, we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER+ /HER2- ) breast carcinoma show distinct repertoires of somatic mutations. Eighteen ER+ /HER2- NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissues were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast carcinomas and/or related to DNA repair. Their mutational repertoire was compared with that of ER+ /HER2- breast carcinomas (n = 240), PAM50-defined luminal breast carcinomas (luminal A, n = 209; luminal B, n = 111) and invasive lobular carcinomas (n = 127) from The Cancer Genome Atlas. NBCs were found to harbour a median of 4.5 (range 1-11) somatic mutations, similar to that of luminal B breast carcinomas (median = 3, range 0-17) but significantly higher than that of luminal A breast carcinomas (median = 3, range 0-18, p = 0.02). The most frequently mutated genes were GATA3, FOXA1, TBX3, and ARID1A (3/18, 17%), and PIK3CA, AKT1, and CDH1 (2/18, 11%). NBCs less frequently harboured PIK3CA mutations than common forms of ER+ /HER2- , luminal A and invasive lobular carcinomas (p < 0.05), and showed a significantly higher frequency of somatic mutations affecting ARID1A (17% versus 2%, p < 0.05) and the transcription factor-encoding genes FOXA1 (17% versus 2%, p = 0.01) and TBX3 (17% versus 3%, p < 0.05) than common-type ER+ /HER2- breast carcinomas. No TP53 somatic mutations were detected in NBCs. As compared with common forms of luminal breast carcinomas, NBCs show a distinctive repertoire of somatic mutations featuring lower frequencies of TP53 and PIK3CA mutations, enrichment for FOXA1 and TBX3 mutations, and, akin to neuroendocrine tumours from other sites, ARID1A mutations. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Biomarcadores Tumorais / Regulação Neoplásica da Expressão Gênica / Carcinoma Neuroendócrino / Carcinoma Lobular Limite: Female / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Biomarcadores Tumorais / Regulação Neoplásica da Expressão Gênica / Carcinoma Neuroendócrino / Carcinoma Lobular Limite: Female / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article