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Tesi etd-03292018-153938


Thesis type
Tesi di dottorato di ricerca
Author
SCARPITTA, ROSA
URN
etd-03292018-153938
Title
Characterization of breast cancer susceptibility genes in men by Next-Generation Sequencing
Settore scientifico disciplinare
MED/03
Corso di studi
SCIENZE CLINICHE E TRASLAZIONALI
Commissione
tutor Dott.ssa Caligo, Maria Adelaide
Parole chiave
  • next generation sequencing
  • BRCA
  • predisposition genes
  • hereditary breast cancer
  • male breast cancer
Data inizio appello
09/04/2018;
Consultabilità
parziale
Data di rilascio
09/04/2021
Riassunto analitico
Male breast cancer (MBC) is a rare disease with an incidence of 1/105 year. MBC tends to occur between 60-70 years old and to express oestrogen and progesterone receptors with occasionally epidermal growth factor receptor 2 amplification. The rarity of MBC has precluded large-scale association studies, thus genetic predisposition remain not well understood. <br>In order to better define genetic risk factors in men, a germline investigation in 81 MBC cases was performed through the screening of 24 genes involved in breast cancer predisposition, genome stability maintenance and DNA repair mechanisms by Next Generation Sequencing. <br>Clinical pathological data and family history of 81 MBC cases were collection revealed an average age of onset was 61.3 years and breast cancer family history in 35 cases. Overall, our genetic screening let to attribute a genetic cause to breast cancer in 23% of cases. In total, 19 patients carried a pathogenic mutation in 4 genes: BRCA2, BRIP1, MUTYH and PMS2. As expected, a positive family history is a strong predictor of germline BRCA2 mutations. Moreover, 14 variants of unknown clinical significance (VUS) in 9 genes (BARD1, BRCA1, BRCA2, BRIP1, CHEK2, ERCC1, NBN, PALB2, PMS1) were predicted as potentially pathogenic by in-silico analysis leading to 40% the mutation detection rate. Understanding the potential pathogenicity of VUS represents an extremely urgent question for the management of breast cancer risk in MBC cases and their own families.
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