Somatic mutations in the Notch, NF-KB, PIK3CA, and Hedgehog pathways in human breast cancers - PubMed (original) (raw)
Somatic mutations in candidate breast cancer genes. Known and novel somatic mutations in candidate breast cancer genes are indicated in their respective protein domain structures. Tumor DNA was extracted from 96 primary human breast tumors, whereas patient-matched normal DNA was derived from blood or adjacent normal tissues. Human genome sequences (hg17 build 35.1), transcript coordinates (RefSeq release 16, March 2006), and single nucleotide polymorphisms were obtained from the UCSC Santa Cruz Genome Bioinformatics Site (
). The ~3.4 million single nucleotide polymorphisms (SNPs) of dbSNP (release 125) that were validated in the HapMap project were used to exclude known polymorphisms, as were rare constitutional variants previously observed by our group in other sequencing studies (Jones et al, 2008; Parsons et al, 2008). PCR, sequencing reactions, and mutational analyses using Mutation Surveyor software (SoftGenetics LLC) were performed as described (Sjöblom et al, 2006). Filled symbols, mutations observed in the present study. Open symbols above domain structure, mutations previously observed in breast cancers in Sjöblom et al. (2006) or Wood et al. (2007). Open symbols below domain structure, cancer-derived mutations present in COSMIC or previously observed in colorectal, pancreatic, or brain tumors (Jones et al, 2008; Parsons et al, 2008). Black triangles, missense mutations. Blue triangles, synonymous mutations. Purple triangles, nonsense mutations. Red triangles, frameshift mutations. Red diamonds, splice site mutations. Domain name abbreviations: AMP BD, AMP-binding enzyme; ANFlig BD, ANF receptor family ligand binding region; ANK, Ankyrin repeat; ArfGAP, ARF GTPase-activating proteins domain; ARM, Armadillo/beta-catenin-like repeat; Cys rich, Cysteine-rich domain; C2, C2 domain; Death, Death domain; Disin, Disintegrin domain; DMAP1 BD, DMAP1-binding domain; EGF, EGF-like domain; FerB, Central domain B in proteins of the Ferlin family; Gln rich, Glutamine-rich; Gly rich, Glycine-rich domain; HLH, Helix-loop-helix domain; IBB, Importin beta binding domain; IPT, Ig-like, plexins, transcription factors domain; KH, K homology RNA binding domain; Lig chan, Ligand-gated ion channel; LNR, Lin-12/Notch repeat; LZ, Leucine zipper; MEPRO, ADAM type metalloprotease domain; NBD, NEMO-binding domain; NOD, Notch protein; NODP, Notch protein; PH, Pleckstrin homology domain; PIPLC, Phosphatidylinositol-specific phospholipase X-box domain; Pro rich, Proline-rich domain; Ras, Ras family; RHD, Rel homology transcription factor domain; STK, Serine/Threonine protein kinase domain; Trm, Transmembrane helices; Ub, Ubiquitin-like domain; Znf, Zinc finger domain.