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PLOS Papers on TB Resistance, Squamous Cell Carcinoma Risk, MicroRNAs in SCC

In PLOS Genetics, researchers from France, Canada, and other international sites share findings from a genome-wide association study searching for host factors that help individuals avoid infection with the tuberculosis (TB)-causing pathogen Mycobacterium tuberculosis. The team compared array-based genotypes in more than 350 M. tuberculosis individuals from a TB-endemic area in southern Vietnam with genotyping profiles for 185 household contacts of those cases who appeared to be TB-negative based on tuberculin skin testing and immune assays, identifying a chromosome 10 locus with genome-wide significant ties to protection from M. tuberculosis infection. The same locus appeared to protect against TB in cohorts in France and South Africa, the authors note, while their follow-up analyses provided clues to the possible immune effects of the variant cluster found.

An international team led by investigators in France finds loci that appear to coincide with increased risk of squamous cell carcinomas of the "aerodigestive tract" — a region encompassing the oral cavity to the lungs — for another paper in PLOS Genetics. By bringing together data for 13,887 cases and almost 62,000 controls from prior GWAS focused on squamous cell carcinomas of the esophagus, larynx, oropharynx, or lung, the researchers narrowed in on a previously unappreciated risk locus near the TMEM273 gene on chromosome 3, along with pleiotropy at known risk sites and new loci showing shakier ties to aerodigestive tract squamous cell carcinoma on chromosomes 1, 5, and 19. They note that genes from DNA damage and epigenetic pathways appeared to be over-represented in a subsequent gene-based analysis of variants identified in the GWAS meta-analysis. "Our results suggest some overlap in the genetic factors influencing the risk of aerodigestive squamous cell carcinomas in European populations," the authors report, "and highlights the importance of cross-cancer studies."

For a paper in PLOS One, investigators in Japan take a look at the small RNA features that distinguish squamous cell carcinomas in the lung from those found in the metastatic lung tumors or in squamous cell carcinomas originating in the head and neck. The team did small RNA sequencing on formalin-fixed paraffin-embedded samples from 14 individuals with lung squamous cell carcinoma, metastatic lung cancer, or head and neck squamous cell carcinoma, uncovering 13 microRNAs that appeared to be differentially expressed in the three cancer types considered. When the authors attempted to validate half a dozen of the miRNAs, they found four miRNAs with higher-than-usual levels in squamous cell carcinomas of the lung, including several miRNAs that were over-represented in extracellular vesicles in blood serum samples.