This is, to our knowledge, the largest single report of diagnostic testing for germline p53 mutations, yielding practical mutation prevalence tables and suggesting clinical utility of classic LFS and Chompret criteria for identifying a subset of cancer-prone families with p53 germline mutations, with important implications for diagnosis and management.

Background: Large rearrangements account for 8% to 15% of deleterious BRCA mutations, although none have been characterized previously in individuals of Mexican ancestry. Methods: DNA from 106 Hispanic patients without an identifiable BRCA mutation by exonic sequence analysis was subjected to multiplexed quantitative differential PCR. One case of Native American and African American ancestry was identified via multiplex ligation-dependent probe amplification. Long-range PCR was used to confirm deletion events and to clone and sequence genomic breakpoints. Splicing patterns were derived by sequencing cDNA from reverse transcription-PCR of lymphoblastoid cell line RNA. Haplotype analysis was conducted for recurrent mutations. Results: The same deletion of BRCA1 exons 9 through 12 was identified in five unrelated families. Long-range PCR and

ERMLINE BRCA1 OR BRCA2 gene mutations significantly increase a woman's risk of breast cancer (50%-85%) and ovarian cancer (16%-50%). 1-5 Identifying women who have had BRCAassociated breast cancer is important because the risk of a new primary breast cancer within 10 years following initial diagnosis is as high as 40% in the absence of oophorectomy or tamoxifen treatment. 6 The corresponding 10-year risk of ovarian cancer is also substantial (6%-12%). 7 Limited-stage breast cancer patients who carry a BRCA gene mutation are offered the option of riskreducing mastectomy, and oophorectomy is recommended. 8,9 Documented efficacy of screening and risk reduction interventions provides evidence for individualized risk management advice, making genetic cancer risk assessment (GCRA) a component of medically necessary care. 10,11 Identifying appropriate candidates for GCRA is challenging. The general consensus (eg, American College of Medical Genetics, National Comprehensive Cancer Network 11-14) is that BRCA testing is not appropriate for unaffected women in the general population, but there is less clarity in this re-For editorial comment see p 2637.