A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. Implications for presymptomatic testing and screening

作者：Donna M. Shattuck-Eidens · 发表于：JAMA · 年份：1995 · DOI：10.1001/jama.273.7.535 · 被引用次数：327 · 研究领域：BRCA gene mutations in cancer、DNA Repair Mechanisms、Ovarian cancer diagnosis and treatment

Objectives. —To report the initial experience of an international group of investigators in identifying mutations in theBRCA1breast and ovarian cancer susceptibility gene, to assess the spectrum of such mutations in samples from patients with different family histories of cancer, and to determine the frequency of recurrent mutations. Design. —Nine laboratories in North America and the United Kingdom tested forBRCA 1mutations in DNA samples obtained from a total of 372 unrelated patients with breast or ovarian cancer largely chosen from high-risk families. Three of these laboratories also analyzed a total of 714 additional samples from breast or ovarian cancer cases, including 557 unselected for family history, for two specific mutations that had been found to recur in familial samples. Participants. —A total of 1086 women with either breast or ovarian cancer. Main Outcome Measure. —The detection of sequence variation in patients' DNA samples that is not found in sets of control samples. Results. —BRCA 1mutations have now been identified in a total of 80 patient samples. Thirty-eight distinct mutations were found among 63 mutations identified through a complete screen of theBRCA 1gene. Three specific mutations appeared relatively common, occurring eight, seven, and five times, respectively. When specific tests for the two most common mutations were performed in larger sets of samples, they were found in 17 additional patients. Mutations predicted to result in a truncated prote...