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Combined targeted DNA and RNA sequencing of advanced NSCLC in routine molecular diagnostics: Analysis of the first 3,000 Heidelberg cases
Author(s) -
Volckmar AnnaLena,
Leichsenring Jonas,
Kirchner Martina,
Christopoulos Petros,
Neumann Olaf,
Budczies Jan,
Morais de Oliveira Cristiano Manuel,
Rempel Eugen,
Buchhalter Ivo,
Brandt Regine,
Allgäuer Michael,
Talla Suranand Babu,
von Winterfeld Moritz,
Herpel Esther,
Goeppert Benjamin,
Lier Amelie,
Winter Hauke,
Brummer Tilman,
Fröhling Stefan,
Faehling Martin,
Fischer Jürgen R.,
Heußel Claus Peter,
Herth Felix,
Lasitschka Felix,
Schirmacher Peter,
Thomas Michael,
Endris Volker,
Penzel Roland,
Stenzinger Albrecht
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32133
Subject(s) - stk11 , ros1 , fusion gene , medicine , crizotinib , molecular diagnostics , kras , dna sequencing , oncology , computational biology , lung cancer , targeted therapy , gene , cancer , bioinformatics , biology , genetics , adenocarcinoma , colorectal cancer , malignant pleural effusion
Tyrosine kinase inhibitors currently confer the greatest survival gain for nonsmall cell lung cancer (NSCLC) patients with actionable genetic alterations. Simultaneously, the increasing number of targets and compounds poses the challenge of reliable, broad and timely molecular assays for the identification of patients likely to benefit from novel treatments. Here, we demonstrate the feasibility and clinical utility of comprehensive, NGS‐based genetic profiling for routine workup of advanced NSCLC based on the first 3,000 patients analyzed in our department. Following automated extraction of DNA and RNA from formalin‐fixed, paraffin‐embedded tissue samples, parallel sequencing of DNA and RNA for detection of mutations and gene fusions, respectively, was performed using PCR‐based enrichment with an ion semiconductor sequencing platform. Overall, 807 patients (27%) were eligible for currently approved, EGFR‐/BRAF‐/ALK‐ and ROS1‐directed therapies, while 218 additional cases (7%) with MET , ERBB2 (HER2 ) and RET alterations could potentially benefit from experimental targeted compounds. In addition, routine capturing of comutations, e.g. TP53 (55%), KEAP1 (11%) and STK11 (11%), as well as the precise typing of fusion partners and involved exons in case of actionable translocations including ALK and ROS1 , are prognostic and predictive tools currently gaining importance for further refinement of therapeutic and surveillance strategies. The reliability, low dropout rates (<5%), minimal tissue requirements, fast turnaround times (6 days on average) and lower costs of the diagnostic approach presented here compared to sequential single‐gene testing, highlight its practicability in order to support individualized decisions in routine patient care, enrollment in molecularly stratified clinical trials, as well as translational research.