| 1. |
- Lin, Jimmy, et al.
(författare)
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A multidimensional analysis of genes mutated in breast and colorectal cancers
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:9, s. 1304-1318
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Tidskriftsartikel (refereegranskat)abstract
- A recent study of a large number of genes in a panel of breast and colorectal cancers identified somatic mutations in 1149 genes. To identify potential biological processes affected by these genes, we examined their putative roles based on sequence similarity, membership in known functional groups and pathways, and predicted interactions with other proteins. These analyses identified functional groups and pathways that were enriched for mutated genes in both tumor types. Additionally, the results pointed to differences in molecular mechanisms that underlie breast and colorectal cancers, including various intracellular signaling and metabolic pathways. These studies provide a multidimensional framework to guide further research and help identify cellular processes critical for malignant progression and therapeutic intervention.
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| 2. |
- Robinson, Kristina Lagerstedt, et al.
(författare)
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Lynch syndrome (hereditary nonpolyposis colorectal cancer) diagnostics
- 2007
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 99:4, s. 291-299
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Tidskriftsartikel (refereegranskat)abstract
- Background Preventive programs for individuals who have high lifetime risks of colorectal cancer may reduce disease morbidity and mortality. Thus, it is important to identify the factors that are associated with hereditary colorectal cancer and to monitor the effects of tailored surveillance. In particular, patients with Lynch syndrome, hereditary nonpolyposis colorectal cancer (HNPCC), have an increased risk to develop colorectal cancer at an early age. The syndrome is explained by germline mutations in DNA mismatch repair (MMR) genes, and there is a need for diagnostic tools to preselect patients for genetic testing to diagnose those with HNPCC. Methods Patients (n = 112) from 285 families who were counseled between 1990 and 2005 at a clinic for patients at high risk for HNPCC were selected for screening to detect mutations in MMR genes MLH1, MSH2, MSH6, and PMS2 based on family history, microsatellite instability (MSI), and immunohistochemical analysis of MMR protein expression. Tumors were also screened for BRAF V600E mutations; patients with the mutation were considered as non-HNPCC. Results Among the 112 patients who were selected for screening, 69 had germline MMR mutations (58 pathogenic and 11 of unknown biologic relevance). Sixteen of the 69 mutations (23%) were missense mutations. Among patients with MSI-positive tumors, pathogenic MMR mutations were found in 38 of 43 (88%) of patients in families who met Amsterdam criteria and in 13 of 22 (59%) of patients in families who did not. Among patients with MSI-negative tumors, pathogenic MMR mutations were found in 5 of 17 (29%) of families meeting Amsterdam criteria and in 1 of 30 (3%) of non-Amsterdam families with one patient younger than age 50 years. In three patients with MSI-negative tumors who had pathogenic mutations in MLH1 or MSH6, immunohistochemistry showed loss of the mutated protein. Conclusion Our findings suggest that missense MMR gene mutations are common in HNPCC and that germline MMR mutations are also found in patients with IVISI-negative tumors.
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| 3. |
- Wood, Laura D, et al.
(författare)
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The genomic landscapes of human breast and colorectal cancers.
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 318:5853, s. 1108-1113
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Tidskriftsartikel (refereegranskat)abstract
- Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.
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