Mapping of actionable mutations to histological subtype domains in lung adenocarcinoma: implications for precision medicine

摘要: // Gavin M. Wright 1 , Hongdo Do 2 Jonathan Weiss Naveed Z. Alam Vivek Rathi 3 Marzena Walkiewicz 4 Thomas John Prudence A. Russell Alexander Dobrovic University of Melbourne Department Surgery, St Vincent’s Hospital Melbourne, Victoria, Australia. Translational Genomics and Epigenomics Laboratory Ludwig Institute for Cancer Research Olivia Newton-John Wellness Centre Heidelberg, Anatomical Pathology Research, 5  Pathology, Correspondence: Wright, email: Keywords : BRAF, EGFR, KRAS, high resolution melting, polymerase chain reaction, tumor heterogeneity. Received Febuary 25, 2014 Accepted March 20, Published 22, Abstract Precision medicine depends on the accurate identification actionable mutations in a sample. It is unknown how heterogeneous distribution such can be tumor. Morphological (i.e. histopathological) heterogeneity well described lung adenocarcinoma has been specifically recognized most recent official clinico-pathological classification. The predominant subtype present now used to classify each adenocarcinoma. No molecular profile exists explain intratumoral differences morphology, despite consistently observed association between specific subtypes poorer survival. Given proposal stratifying into differing metastatic potential, we questioned assumption that major are uniformly throughout tumors; especially those showing discrete different subtypes. We selected formalin-fixed paraffin embedded specimens showed areas subtypes, extracted DNA samples from screened hotspot regions EGFR KRAS BRAF genes using melting. Sanger sequencing was confirm all identified mutations. Chromogenic situ hybridization (CISH) identify mutant allele imbalances tumors with Interestingly, found could confined morphological domains higher grade. On other hand, were through histological consistent driver status this mutation. Intratumoral implications tumorigenesis, chemoresistance role histopathology screening precision medicine. This study not only confirms mutational does occur, but also it associated morphologically distinct some tumors. From practical perspective, small biopsies may adequately represent tumor’s full profile, particularly later arising prognostically important as genes.