| Autor: |
Aretini P; Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy., Presciuttini S; Dipartimento di Ricerca Traslazionale e Nuove Tecnologie in Medicina e Chirurgia, Università di Pisa, 56126 Pisa, Italy., Pastore A; Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy.; Laboratorio NEST, Scuola Normale Superiore, 56126 Pisa, Italy., Galli A; Istituto di Fisiologia Clinica, Consiglio Nazionale delle Ricerche (CNR), 56124 Pisa, Italy., Panepinto S; Laboratorio di Genetica Molecolare, Azienda Ospedaliera Universitaria Pisana, 56126 Pisa, Italy., Tancredi M; Laboratorio di Genetica Molecolare, Azienda Ospedaliera Universitaria Pisana, 56126 Pisa, Italy., Ghilli M; Breast Unit, Azienda Ospedaliera Universitaria Pisana, 56126 Pisa, Italy., Guglielmi C; Laboratorio di Genetica Molecolare, Azienda Ospedaliera Universitaria Pisana, 56126 Pisa, Italy., Sidoti D; Laboratorio di Genetica Molecolare, Azienda Ospedaliera Universitaria Pisana, 56126 Pisa, Italy., Congregati C; Genetica Medica, Azienda Ospedaliera Universitaria Pisana, 56126 Pisa, Italy., Caligo MA; Laboratorio di Genetica Molecolare, Azienda Ospedaliera Universitaria Pisana, 56126 Pisa, Italy. |
| Abstrakt: |
Approximately 30-50% of hereditary breast and ovarian cancer (HBOC) is due to the presence of germline pathogenic variants in the BRCA1 (OMIM 113705) and BRCA2 (OMIM 600185) onco-suppressor genes, which are involved in DNA damage response. Women who carry pathogenic BRCA1 variants are particularly likely to develop breast cancer (BC) and ovarian cancer (OC), with a 45-79 percent and 39-48 percent chance, respectively. The BRCA1 c.4096+1G>A variant has been frequently ascertained in Tuscany, Italy, and it has also been detected in other Italian regions and other countries. Its pathogenetic status has been repeatedly changed from a variant of uncertain significance, to pathogenic, to likely pathogenic. In our study, 48 subjects (38 of whom are carriers) from 27 families were genotyped with the Illumina OncoArray Infinium platform (533,531 SNPs); a 20 Mb region (24.6 cM) around BRCA1 , including 4130 SNPs (21 inside BRCA1 ) was selected for haplotype analysis. We used a phylogenetic method to estimate the time to the most recent common ancestor (MRCA) of BRCA1 c.4096+1G>A founder pathogenic variant. This analysis suggests that the MRCA lived about 155 generations ago-around 3000 years ago. |
