In Cancer Discovery this week, researchers in Maryland and Massachusetts say that HIF1-alpha could function as a 14q kidney cancer suppressor gene. Kidney cancers often delete chromosomes 3p and 14q, which contain tumor suppressor genes, the authors write. For this study, the team identified focal, homozygous deletions of the HIF1-alpha locus on chromosome 14q in clear renal carcinoma cell lines — wild-type HIF1-alpha suppresses renal carcinoma growth, but the altered loci don't. In addition, the team says, down-regulation of HIF1-alpha in HIF1-alpha-proficient cell lines promotes tumor growth. "HIF1-alpha activity is diminished in 14q-deleted kidney cancers, and all somatic HIF1-alpha mutations identified in kidney cancers tested to date are loss of function," the authors write. "Therefore, HIF1-alpha has the credentials of a kidney cancer suppressor gene."
Also in Cancer Discovery this week, researchers in the UK present a study on functional viability profiles of breast cancer. The development of targeted therapeutics for cancer is driven by the identification of tumor-specific mutations, but the large number of genetic changes present makes it difficult to determine which ones are necessary for maintaining the disease and which ones are coincidental, the authors write. To address this issue, the team carried out a functional genetic screen in more than 30 commonly used models of breast cancer to identify genes critical to the growth of different subtypes of the disease. "In particular, we describe potential new therapeutic targets for PTEN-mutated cancers and for estrogen receptor-positive breast cancers," the researchers write. "We also show that large-scale functional profiling allows the classification of breast cancers into subgroups distinct from established subtypes." Using high-throughput RNA interference screening of a series of genes, the team was able to generate comprehensive functional viability profiles for a wide panel of commonly used breast cancer models.