Lin Lin

TL;DR: The identification of a set of genes that predict survival in early-stage lung adenocarcinoma allows delineation of a high-risk group that may benefit from adjuvant therapy.

TL;DR: A peak of genomic amplification on chromosome 3q26.33 found in squamous cell carcinomas of the lung and esophagus contains the transcription factor gene SOX2, which is necessary for normal esophageal squamous development, promotes differentiation and proliferation of basal tracheal cells and cooperates in induction of pluripotent stem cells.

Abstract: The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With a 5-year survival rate of ~15%, the identification of new therapeutic targets for EAC is greatly important. We analyze the mutation spectra from whole-exome sequencing of 149 EAC tumor-normal pairs, 15 of which have also been subjected to whole-genome sequencing. We identify a mutational signature defined by a high prevalence of A>C transversions at AA dinucleotides. Statistical analysis of exome data identified 26 significantly mutated genes. Of these genes, five (TP53, CDKN2A, SMAD4, ARID1A and PIK3CA) have previously been implicated in EAC. The new significantly mutated genes include chromatin-modifying factors and candidate contributors SPG20, TLR4, ELMO1 and DOCK2. Functional analyses of EAC-derived mutations in ELMO1 identifies increased cellular invasion. Therefore, we suggest the potential activation of the RAC1 pathway as a contributor to EAC tumorigenesis.

TL;DR: A mutational signature defined by a high prevalence of A>C transversions at AA dinucleotides is identified and the potential activation of the RAC1 pathway is suggested as a contributor to EAC tumorigenesis.

TL;DR: Genomic features that were common and distinct to various gut-derived adenocarcinomas were defined, potentially informing novel opportunities for targeted therapeutic interventions and suggesting the potential use of genomic amplifications as biomarkers to guide therapy of gastric and esophageal cancers.