Objective: To investigate the BRCA1 gene in hereditary breast and ovarian cancer, early-onset breast cancer and sporadic ovarian cancer.
Methods: The exons of 2, 11 and 20 of BRCA1 gene were analyzed. Polymerase chain reaction-single strand conformation analysis (PCR-SSCP) and PCR-SSCP combined by restriction enzymes were used to screen for mutations. Mutations were further indentified by sequencing. The loss of heterozygosity (LOH) were also investigated at the BRCA1 genetic loci D17S855 in 10 hereditary ovarian cancer.
Results: A insertion mutation was detected in H7. "C" was inserted at nucleotide 797. It would result in truncation of the BRCA1 protein at codon 277. A missense mutation was detected in an early-onset breast cancer (diagnosed at age 24). At nucleotide position 3732, the substitution of a "G" to a "C" in codon 1205 changes a Gly to a Arg. A missense mutation were also detected in three sporadic ovarian cancers. At nucleotide position 2051, the substitution of a "T" to a "G" in codon 644 changes a Cys to a Trp. H3 and H7 patients show LOH.
Conclusions: BRCA1 gene has an important effect in Chinese hereditary breast and ovarian cancer, its effect on early-onset breast cancer and sporadic ovarian cancer are still to be studied. BRCA1 gene is a tumor-suppressor gene.