heterozygous mutations in dna repair genes and hereditary breast cancer a question of power在dna修复基因的杂合突变和遗传性乳腺癌权力的问题.pdfVIP

Perspective Heterozygous Mutations in DNA Repair Genes and Hereditary Breast Cancer: A Question of Power 1 2 Nathan A. Ellis *, Kenneth Offit * 1 Department of Pediatrics and the Institute of Human Genetics, University of Illinois at Chicago, Chicago, Illinois, United States of America, 2 Department of Medicine, Memorial Sloan-Kettering Cancer Center, Program in Cancer Biology and Genetics, Sloan-Kettering Institute, New York, New York, United States of America The emerging technology of massively applications of new sequencing technolo- multiple developmental abnormalities (small parallel DNA sequencing has had a major gies to the search for the ‘‘missing heri- size and congenital defects of the dermal, impact on progress in genomics and tability’’ in hereditary breast cancer. In immune, skeletal, and reproductive systems), personalized medicine [1]. Most recently, Thompson et al., the authors performed striking DNA repair defects and genomic DNA sequencing of whole exomes (com- exome sequencing of multiple breast cancer instability in the somatic cells, and enormous plete coding regions of the human ge- cases from a small number of families (33 predisposition to the development of various nome) has revealed the genetic basis of persons in 15 families) in whom BRCA1 and cancers (Figure 1) [18,19]. Bi-allelic muta- many previously-not-localized Mendelian BRCA2 mutations had been excluded, tions in FANCC and BLM result in FA and traits [2]. In diseases where the underlying and they focused on mutations that are BS, respectively, whereas in Thompson et al. genetic basis is more dilute