Abstract:
:Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 are responsible for a large proportion of familial breast cancer cases, and therefore, BRCA1 and BRCA2 genetic testing has become increasingly common in clinical practice. However, variants of uncertain significance (VUS) have been detected in 16.3% of Japanese patients suspected of having hereditary breast and ovarian cancers. The clinical importance of VUS is unknown, and their incidence has led to issues in risk counseling, assessment and treatment of cancer patients. In the present study, we performed functional analyses of two VUS in BRCA1, A1752G and Y1853C that were detected in two independent breast cancer patients who were suspected of having hereditary breast cancer. Segregation analysis revealed that Y1853C, but not A1752G, was cosegregated in affected family members. Conservation, transcription and structure analyses also supported the pathogenic potential of Y1853C. Detailed segregation and in silico and in vitro analyses will enhance our understanding of VUS and improve the management of cancer patients and their families.
journal_name
J Hum Genetjournal_title
Journal of human geneticsauthors
Kawaku S,Sato R,Song H,Bando Y,Arinami T,Noguchi Edoi
10.1038/jhg.2013.71subject
Has Abstractpub_date
2013-09-01 00:00:00pages
618-21issue
9eissn
1434-5161issn
1435-232Xpii
jhg201371journal_volume
58pub_type
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