title: Rapid identification of somatic mutations in colorectal and breast cancer tissues using mismatch repair detection (MRD).
abstract: Mismatch repair detection (MRD) was used to screen 93 matched tumor-normal sample pairs and 22 cell lines for somatic mutations in 30 cancer relevant genes. Using a starting amount of only 150 ng of genomic DNA, we screened 102 kb of sequence for somatic mutations in colon and breast cancer. A total of 152 somatic mutations were discovered, encompassing previously reported mutations, such as BRAF V600E and KRAS G12S, G12V, and G13D, as well as novel mutations, including some in genes in which somatic mutations have not previously been reported, such as MAP2K1 and MAP2K2. The distribution of mutations ranged widely within and across tumor types. The functional significance of many of these mutations is not understood, with patterns of selection only evident in KRAS and BRAF in colon cancer. These results present a novel approach to high-throughput mutation screening using small amounts of starting material and reveal a mutation spectrum across 30 genes in a large cohort of breast and colorectal cancers.
authors.affiliation: Molecular Profiling-Pharmacogenomics, Pfizer Global Research and Development, Groton Laboratories, Groton, Connecticut, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Bentivegna
authors.forename: Jianbiao
authors.initials: J
authors.lastname: Zheng
authors.forename: Eugeni
authors.initials: E
authors.lastname: Namsaraev
authors.forename: Victoria E H
authors.initials: VE
authors.lastname: Carlton
authors.forename: Adam
authors.initials: A
authors.lastname: Pavlicek
authors.forename: Martin
authors.initials: M
authors.lastname: Moorhead
authors.forename: Farooq
authors.initials: F
authors.lastname: Siddiqui
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Wang
authors.forename: Liana
authors.initials: L
authors.lastname: Lee
authors.forename: James S
authors.initials: JS
authors.lastname: Ireland
authors.forename: Kent
authors.initials: K
authors.lastname: Suyenaga
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Willis
authors.forename: Malek
authors.initials: M
authors.lastname: Faham
authors.forename: Albert B
authors.initials: AB
authors.lastname: Seymour
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics*; D053843:DNA Mismatch Repair; D004252:DNA Mutational Analysis / Q000379:methods*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation
chemical_list: D004273:DNA, Neoplasm