In the early, online edition of the Proceedings of the National Academy of Sciences, a team from Japan and the US describe recurrent deletions involving a portion of chromosome 3 in individuals with mesothelioma. Using a custom array comparative genomic hybridization array, the researchers assessed nearly three dozen malignant mesothelioma biopsy samples, searching for copy number changes affecting the chromosome 3p21 region — a site containing more than 250 genes. Their analysis uncovered small deletions affecting both alleles of 46 genes. The inactivation of four genes — SETD2, BAP1, PBRM1, and SMARCC1 — that have been implicated in cancer in the past were scrutinized more carefully by targeted sequencing.
A team from the US and Russia takes a look at the ties between mutation density, cytotoxic T cell immune expression, expression of immune checkpoint blockade genes such as PD-1, PD-L1, and PD-L2, and cancer outcomes in individuals with melanoma or other cancer types. Using RNA sequence, mutation profile, and other data from the Cancer Genome Atlas, the researchers analyzed nine solid tumor types. PD-L2 expression appeared more closely linked to immune cell activity than was PD-L1 expression in some cancers, the authors note. Mutational load, on the other hand, "was not immediately related to inflammation in any tumor type studied, and was inferior to an inflamed tumor microenvironment for predicting survival in patients with metastatic melanoma," the researchers say.
Finally, researchers from the US, Singapore, New Zealand, and the UK present findings from a mouse transposon mutagenesis screen for genes that act alongside PTEN gene mutations to spur triple-negative breast cancer. The team did Sleeping Beauty mutagenesis in a transgenic mouse model missing PTEN, uncovering mutations in a dozen potential driver genes — including six known tumor suppressor genes — and additional genes suspected of spurring cancer progression. In a series of follow-up experiments in mouse models and cell lines, the group validated ties between triple-negative breast cancer and eight tumor suppressor genes.