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Prevalence and potential biological role of TERT amplifications in ALK translocated adenocarcinoma of the lung
Author(s) -
Alidousty Christina,
Duerbaum Nicolai,
WagenerRyczek Svenja,
Baar Till,
Martelotto Luciano G,
Heydt Carina,
Siemanowski Janna,
Holz Barbara,
Binot Elke,
Fassunke Jana,
MerkelbachBruse Sabine,
Wolf Jürgen,
Kron Anna,
Buettner Reinhard,
Schultheis Anne M
Publication year - 2021
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.14256
Subject(s) - context (archaeology) , lung cancer , adenocarcinoma , gene duplication , copy number variation , cancer , gene , cancer research , anaplastic lymphoma kinase , biology , medicine , oncology , gene dosage , disease , genetics , genome , gene expression , paleontology , malignant pleural effusion
Aims The advent of specific ALK‐targeting drugs has radically changed the outcome of patients with ALK translocated non‐small‐cell lung cancer (NSCLC). However, emerging resistance to treatment with ALK inhibitors in these patients remains a major concern. In previous studies, we analysed two ALK+ patient cohorts ( TP53 wild‐type/ TP53 mutated) in terms of copy number alterations. All patients belonging to the TP53 wild‐type group had mainly genetically stable genomes, with one exception showing chromosomal instability and amplifications of several gene loci, including TERT . Here, we aimed to determine the prevalence of TERT amplifications in these ALK+ lung cancer patients by analysing an independent cohort of 109 ALK translocated cases. We further analysed the copy numbers of numerous cancer‐relevant genes and other genetic aberrations. Methods and results The prevalence of TERT amplifications was determined by means of FISH analyses. Copy numbers of 87 cancer‐relevant genes were determined by NanoString nCounter ® technology, FoundationOne ® and lung‐specific NGS panels in some of these TERT ‐amplified samples, and clinical data on patients with TERT ‐amplified tumours were collected. Our data revealed that five (4.6%) of all 109 analysed ALK+ patients harboured amplification of TERT and that these patients had genetically unstable genomes. Conclusions Our preliminary study shows that ALK + adenocarcinomas should be evaluated in the context of their genomic background in order to more clearly understand and predict patients' individual course of disease.