Researchers led by Ming Guan from Shanghai Medical School report in Modern Pathology that DLC1 methylation and mutations in PIK3CA may play important roles in the development of Paget's disease, a rare cutaneous malignant neoplasm of the breast. They examined tissue biopsies from 132 patients with extramammary Paget's disease for methylation levels of DLC1 CpG islands using both high-resolution melting analysis and bisulfite DNA sequencing, and for PIK3CA mutations using direct DNA sequencing. From that, they "found a high prevalence of downregulation and hypermethylation of the DLC1 gene in cases of this rare disease (33 and 39%, respectively). In addition, activating PIK3CA mutations were detected in 24% of the extramammary Paget's disease cases." This, the researchers add, shows "evidence that epigenetic and genetic alterations are common in extramammary Paget's disease and may be involved in the disease pathogenesis."
Also in Modern Pathology, the National University of Singapore's Chee-Seng Ku and colleagues review how advances in sequence capture and next-generation sequencing have led to progress in understanding familial diseases and how such approaches can be applied to better characterize colorectal cancer type X, a familial cancer. "In the context of familial colorectal cancer type X, we believe that the disease model and its genetic basis are likely to become more apparent when the approaches that we have outlined and discussed are applied in practice," Ku et al. write. "This should facilitate the iterative interrogation of the genetics of familial colorectal cancer type X and other familial cancers of similar nature before embarking on either a comprehensive genome-wide association studies or whole-genome sequencing approach."