Connection Between Epigenome, Selective Mutability, Evolution, and Human Disease
Li, Harris et al., PLoS Genetics
Researchers at the Baylor College of Medicine and elsewhere propose a "connection between the epigenome, selective mutability, evolution, and human disease" based on the findings of their study on associations of structural mutability with germline DNA methylation and with non-allelic homologous recombination mediated by low-copy repeats. "Combined evidence from four human sperm methylome maps, human genome evolution, structural polymorphisms in the human population, and previous genomic and disease studies consistently points to a strong association of germline hypomethylation and genomic instability," the Baylor-led team writes.
This Week in Experimental and Molecular Pathology
Researchers led by Chirayu Auewarakul from Siriraj Hospital in Bangkok, Thailand, report in Experimental and Molecular Pathology on BCR-ABL kinase domain mutations in Southeast Asian patients with chronic myeloid leukemia. Mutations in the BCR-ABL kinase domain are associated with resistance to tyrosine kinase inhibitors used to treat CML. Using high-performance liquid chromatography and direct sequencing, the researchers studies the mutation status of 80 treatment-naïve CML patients and 91 patients receiving first-generation or second-generation TKI therapy. From this, they found 13 known and 8 novel mutations. "T315I resistant mutation was completely undetectable in this naïve Southeast Asian cohort; its incidence, however, increases with drug exposure," the authors write.
Also in Experimental and Molecular Pathology, Kee Yang Chung from the Yonsei University College of Medicine in Seoul and his colleagues studied the expression pattern of matrix metalloproteinases in cutaneous oncogenesis. In particular, they used immunohistochemical staining and quantitative RT-PCR to examine the expression patterns of MMP-2,-9, MT1-MMP, and TIMP-2 proteins in squamous cell carcinoma, Bowen's disease, and normal samples. "Our results revealed significantly increased MT1-MMP and MMP-2 expression and decreased TIMP-2 expression in cutaneous SCC, and the expression correlated with the invasiveness of SCC cell lines," the authors write. "Therefore, the expression of these factors in cutaneous tumors may serve as an indicator of tumor aggressiveness and invasion."