Whole-exome sequencing and targeted gene sequencing provide insights into the role of PALB2 as a male breast cancer susceptibility gene

Antonio Russo, Piera Rizzolo, Siranoush Manoukian, Valentina Silvestri, Jacopo Azzollini, Paolo Peterlongo, Anna Sara Navazio, Virginia Valentini, Domenico Palli, Laura Ottini, Ines Zanna, Cristina Oliani, Paolo Radice, Maria Grazia Tibiletti, Marco Montagna, Giovanni Chillemi, Veronica Zelli, Piera Rizzolo, Laura Cortesi, Paolo PeterlongoTiziana Castrignanò, Bernard Peissel, Simona Agata, Anna Coppa, Bernardo Bonanni, Giovanna Masala, Alessandra Viel, Giuseppe Giannini, Daniela Barana, Ines Zanna

Risultato della ricerca: Articlepeer review

18 Citazioni (Scopus)


BACKGROUND: Male breast cancer (MBC) is a rare disease whose etiology appears to be largely associated with genetic factors. BRCA1 and BRCA2 mutations account for about 10% of all MBC cases. Thus, a fraction of MBC cases are expected to be due to genetic factors not yet identified. To further explain the genetic susceptibility for MBC, whole-exome sequencing (WES) and targeted gene sequencing were applied to high-risk, BRCA1/2 mutationânegative MBC cases. METHODS: Germ-line DNA of 1 male and 2 female BRCA1/2 mutationânegative breast cancer (BC) cases from a pedigree showing a first-degree family history of MBC was analyzed with WES. Targeted gene sequencing for the validation of WES results was performed for 48 high-risk, BRCA1/2 mutationânegative MBC cases from an Italian multicenter study of MBC. A case-control series of 433 BRCA1/2 mutationânegative MBC and female breast cancer (FBC) cases and 849 male and female controls was included in the study. RESULTS: WES in the family identified the partner and localizer of BRCA2 (PALB2) c.419delA truncating mutation carried by the proband, her father, and her paternal uncle (all affected with BC) and the N-acetyltransferase 1 (NAT1) c.97C>T nonsense mutation carried by the proband's maternal aunt. Targeted PALB2 sequencing detected the c.1984A>T nonsense mutation in 1 of the 48 BRCA1/2 mutationânegative MBC cases. NAT1 c.97C>T was not found in the case-control series. CONCLUSIONS: These results add strength to the evidence showing that PALB2 is involved in BC risk for both sexes and indicate that consideration should be given to clinical testing of PALB2 for BRCA1/2 mutationânegative families with multiple MBC and FBC cases. Cancer 2017;123:210â218. © 2016 American Cancer Society.
Lingua originaleEnglish
pagine (da-a)210-218
Numero di pagine9
Stato di pubblicazionePublished - 2017

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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