Researchers in Vancouver report that their nine-gene panel could determine subtypes of endometrial carcinoma in the Journal of Pathology this week. The researchers sequenced the exons of ARID1A, PPP2R1A, PTEN, PIK3CA, KRAS, CTNNB1, TP53, BRAF, and PPP2R5C in 393 endometrial carcinomas from two large cohorts, and found that each subtype of the cancer had a different mutational profile: high-grade endometrioid cancers have different frequencies of PTEN and TP53 mutations than low-grade ones and serous carcinomas and high-grade endometrioid cancers have different mutational frequencies in PTEN, ARID1A, PPP2R1A, TP53, and CTNNB1. "Although endometrial carcinoma subtype diagnoses and grade are currently used in guiding patient management, mutational analysis is emerging as a realistic option in clinical practice," the researchers write. "In the future, we predict that the mutational classification of endometrial carcinomas will become an important tool in diagnosis, guiding mutation-based targeted treatment decisions."
Also in the Journal of Pathology researchers led by Portugal's Carla Oliveira show that deletions in miR-101 lead to its downregulation, overexpression of EZH2, and dysregulation of E-cadherin dysfunction in gastric cancer. "Our data reinforce the critical role of E-cadherin in GC and pinpoint EZH2 over-expression, as a consequence of miR-101 loci deletion and mature miR-101 down-regulation, as one of the missing mechanisms for E-cadherin inactivation in advanced intestinal GC," Oliveria and her colleagues write. "This strong association suggests that therapeutic intervention based on restoration of miR-101 or pharmacological inhibition of EZH2 may have clinical benefit in patients with intestinal-type GC."