Molecular profiling of lung adenosquamous carcinoma: hybrid or genuine type?

Abstract

Lung adenosquamous carcinoma is a particular subtype of non-small cell lung carcinoma that is defined by the coexistence of adenocarcinoma and squamous cell carcinoma components. The aim of this study was to assess the mutational profile in each component of 16 adenosquamous carcinoma samples from a Caucasian population by a combination of next generation sequencing using the cancer hotspot panel as well as the colon and lung cancer panel and FISH. Identified mutations were confirmed by Sanger sequencing of DNA from cancer cells of each component collected by Laser Capture microdissection. Mutations typical for adenocarcinoma as well as squamous cell carcinoma were identified. Driver mutations were predominantly in the trunk suggesting a monoclonal origin of adenosquamous carcinoma. Most remarkably, EGFR mutations and mutations in the PI3K signaling pathway, which accounted for 30% and 25% of tumors respectively, were more prevalent while KRAS mutations were less prevalent than expected for a Caucasian population. Surprisingly, expression of classifier miR-205 was intermediate between that of classical adenocarcinoma and squamous cell carcinoma suggesting that adenosquamous carcinoma is a transitional stage between these tumor types. The high prevalence of therapy-relevant targets opens new options of therapeutic intervention for adenosquamous carcinoma patients.

Spatial aspects of oncogenic signalling determine the response to combination therapy in slice explants from Kras‐driven lung tumours

“…This extends the finding of prior studies that ascribed altered PI3K–AKT and SRC signalling to Lkb1 loss in Kras ‐driven NSCLC , but we relate this to an alteration in histotype spectra, particularly an increase in ASCs. Interestingly, mutations in the PI3K pathway have been detected specifically in the SCC, but not in the AC, components of clinical ASCs . This implies that PI3K–AKT signalling could indeed drive human squamous tumours, and corroborates findings demonstrating SCC induction following loss of the PTEN negative regulator of PI3K–AKT signalling .…”

miR-29b Mediates NF-κB Signaling in KRAS-Induced Non–Small Cell Lung Cancers

“…Clinical-pathologic characteristics are provided in Supplementary Table S1. Tumor DNA was analyzed for KRAS and EGFR mutations by pyrosequencing or Sanger sequencing as described previously (21). Copy numbers of the miR-29b loci were assessed by qPCR using primer pairs encompassing a region from the pre-miRNA (22) relative to the autosomal reference gene GAPDH (QT02504271, Qiagen).…”

Clinical outcomes of epidermal growth factor receptor tyrosine kinase inhibitors in recurrent adenosquamous carcinoma of the lung after resection

“…These findings implied that ASC is a monoclonal tumor, suggesting that squamous cell carcinomatous and adenocarcinomatous components may derive from common tumor stem cells and subsequently differentiate into separate histological types. In other words, ASC is a transitional stage between ADC and SCC 13,14,19,30,31. It has been supported by a case report, in which a young light ex-smoker with ASC relapsed twice with histological changes (from ASC to pure SCC to pure ADC) 32…”