Genomic landscape of atypical adenomatous hyperplasia reveals divergent modes to lung adenocarcinoma

There is a dearth of knowledge about the pathogenesis of premalignant lung lesions, especially for atypical adenomatous hyperplasia (AAH), the only known precursor for the major lung cancer subtype adenocarcinoma (LUAD). In this study, we performed deep DNA and RNA sequencing analyses of a set of AAH, LUAD and normal tissues. Somatic BRAF variants were found in 5/22 (23%) of AAH patients, 4/5 of whom had matched LUAD with driver EGFR mutations. KRAS mutations were present in all ever-smoker cases in the cohort (18%) exclusive of the cases with BRAF mutations. Integrative analysis revealed profiles expressed in KRAS-mutant cases (UBE2C, REL) and BRAF- mutant cases (MAX) of AAH, or common to both sets of cases (suppressed AXL). Gene sets associated with suppressed anti-tumor (Th1; IL12A, GZMB) and elevated pro-tumor (CCR2, CTLA-4) immune signaling were enriched in AAH development and progression. Our results reveal potentially divergent BRAF or KRAS pathways of AAH and immune dysregulation in the pathogenesis of this pre-malignant lung lesion.

from Cancer via ola Kala on Inoreader http://ift.tt/2y7qYPB
via IFTTT