BRCA1 germline mutations in Indian familial breast cancer.

Germline mutation analysis of BRCA1 gene has demonstrated significant allelic heterogeneity. These differences represent historical influences of migration, population structure and geographic or cultural isolation. To date, there have been no reports of Indian families with mutations in BRCA1. We have screened for mutations in selected coding exons of BRCA1 and their flanking intron regions in three breast or breast and ovarian cancer families with family history of three or more cases of breast cancer under age 45 and/or ovarian cancer at any age. We have also analyzed 10 female patients with sporadic breast cancer regardless of age and family history, as well as 50 unrelated normal individuals as controls. Thus a total of 90 samples were analyzed for BRCA1 mutations using polymerase chain reaction-mediated site directed mutagenesis (PSM) and single stranded conformation polymorphism (SSCP) analysis for various selected exons followed by sequencing of variant bands. Eight point mutations were identified. Two deleterious pathogenic, protein truncating non-sense mutations were detected in exon 11 (E1250X) and exon 20 (E1754X) and six novel and unique amino acid substitutions (F1734S, D1739Y, V1741G, Q1747H, P1749A, R1753K). One complex missense mutation of exon 20 [V1741G; P1749A] was seen in two out of three families and another complex combination of missense and non-sense mutations of the same exon [V1741G; E1754X] was observed in only one family. These complex mutations exist only in breast cancer families but not in control populations of women. Three splice site variants (IVS20+3A>C, IVS20+4A>T, IVS20+5A>T) and two intronic variants (IVS20+21_22insG, IVS20+21T>G) were also detected. In the group of 10 sporadic female patients no mutations were found.

Valarmathi MT ，A A ，Deo SS ，Shukla NK ，Das SN ... -  《-》

Novel germline mutations in breast cancer susceptibility genes BRCA1, BRCA2 and p53 gene in breast cancer patients from India.

Hedau S ，Jain N ，Husain SA ，Mandal AK ，Ray G ，Shahid M ，Kant R ，Gupta V ，Shukla NK ，Deo SS ，Das BC ... -  《BREAST CANCER RESEARCH AND TREATMENT》

[Germline mutation of BRCA1 gene in Polish families with strong aggregation of breast and/or ovarian cancer based on coding sequence analysis using the SSCP method].

Byrski T 《-》

BRCA1 and TP53 mutation spectrum of breast carcinoma in an ethnic population of Kashmir, an emerging high-risk area.

Eachkoti R ，Hussain I ，Afroze D ，Aejazaziz S ，Jan M ，Shah ZA ，Das BC ，Siddiqi MA ... -  《CANCER LETTERS》

BRCA1 germline mutational spectrum in Italian families from Tuscany: a high frequency of novel mutations.

Caligo MA ，Ghimenti C ，Cipollini G ，Ricci S ，Brunetti I ，Marchetti V ，Olsen R ，Neuhausen S ，Shattuck-Eidens D ，Conte PF ，Skolnick MH ，Bevilacqua G ... -  《ONCOGENE》