Weill Cornell Medical College's Siân Jones and her colleagues report in The Journal of Pathology "that point mutations are much less common in low-grade serous tumors of the ovary than in other adult tumors, a finding with interesting scientific and clinical implications." Jones' team applied exome sequencing to the DNA of eight serous carcinoma samples in order to analyze somatic mutations in low-grade carcinomas. They found a small number of mutations in seven of these tumors — a total of 70 somatic mutations in 64 genes — with the eighth case displaying mixed serous, endometrioid features, and a mutator phenotype with 783 somatic mutations. "We validated representative mutations in an additional nine low-grade serous carcinomas and 10 serous borderline tumors, the precursors of ovarian low-grade, serous carcinomas," Jones and her team write.

Also in The Journal of Pathology this week, the London Research Institute's Alvin Lee and his collaborators discuss the role of chromosomal instability (CIN) in multi-drug resistance and the silencing of the ceramide transporter, CERT, which promotes cytotoxic sensitivity. "Using an integrative functional genomics approach, we find that CERT-specific multidrug sensitization is associated with enhanced autophagosome–lysosome flux, resulting from the expression of LAMP2 following CERT silencing in colorectal and HER2 breast cancer cell lines," Lee's team writes. They add that live cell microscopy analysis demonstrates "that CERT depletion induces LAMP2-dependent death of polyploid cells following exit from mitosis in the presence of paclitaxel." They also report data suggesting that "the induction of LAMP2-dependent autophagic flux through CERT targeting may provide a rational approach to enhance multi-drug sensitization and potentiate the death of polyploid cells following paclitaxel exposure to limit the acquisition of CIN and intra-tumour heterogeneity."

Researchers from the Breakthrough Breast Cancer Research Centre characterize the genomic and phenotypic characteristics of papillary carcinomas "to determine whether they would constitute an entity distinct from grade and estrogen receptor (ER)-matched invasive ductal carcinomas of no special type (IDC-NSTs)." After analyzing 49 microdissected papillary carcinomas and 49 microdissected grade and ER-match samples of no special type, the team produced data demonstrating that papillary carcinomas are a homogeneous histological breast cancer type. "The similarities in the genomic profiles of papillary carcinomas and grade- and ER-matched IDC-NSTs suggest that papillary carcinomas may be best positioned as part of the spectrum of ER-positive breast cancers, rather than as a distinct entity," the auuthors write in The Journal of Pathology this week. "Furthermore, the good prognosis of papillary carcinomas may stem from the low rates of lymph node metastasis and p53 expression, low number of gene copy number aberrations and high prevalence of PIK3CA mutations."