In PLOS One, researchers from Georgetown University and elsewhere describe a set of frequently mutated and/or copy number altered genes associated with poor breast cancer outcomes. The team profiled ductal carcinoma in situ samples and took advantage of genomic data on infiltrating ductal carcinoma cases from the Cancer Genome Atlas, looking at the prevalence of cases involving loss or low levels of SYK — a gene suspected of contributing to immunity and cancer risk. In addition to detecting SYK loss in a significant subset of cases, the researchers also identified a set of 55 SYK-interacting genes that appear to provide prognostic information in some of these breast cancer cases. Our sister publication GenomeWeb Daily News has more on the study, here.
As part of a fine-mapping study of a prostate cancer risk locus published in PLOS Genetics, an Institute of Cancer Research-led team detected an apparent synthetic association between common, low penetrance SNPs and a rare, causal contributor to the disease. Using custom arrays, imputation, and/or targeted assays on samples from thousands of individuals with or without prostate cancer, the researchers identified four common SNPs that tag a rare, high risk variant in the HOXB region of chromosome 17. Those involved in the study say their findings offer an example of the way in which heritability may be underestimated when risk predictions are based exclusively on common variants associated with various traits or diseases from genome-wide association studies. For more information, check out a related story from Friday's GWDN.
For another PLOS Genetics study, Mayo Clinic, Translational Genomics Research Institute, and National Cancer Institute researchers report on the candidate drug targets they found through a combination of exome, genome, and transcriptome sequencing experiments on samples from half a dozen individuals with an advanced form of a bile duct cancer called sporadic intrahepatic cholangiocarcinoma. In half of the tumor samples, the group saw translocations involving the FGFR2 gene, prompting the use of FGFR inhibitor treatment in two of the patients. The genomic data also revealed mutations affecting the EGFR pathway in another sporadic intrahepatic cholangiocarcinoma patient, who went into regression following treatment with an EGFR kinase inhibitor.