Focused molecular analysis of small cell lung cancer: feasibility in routine clinical practice. Feasibility in routine clinical practice

Fatma Abdelraouf, Adam Sharp, Manisha Maurya, Debbie Mair, Andrew Wotherspoon, Alex Leary, D. Gonzalez de Castro, Jaishree Bhosle, Ayatallah Nassef, Taghrid Gaafar, Sanjay Popat, Timothy A. Yap, Mary O'Brien

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Abstract

Background: There is an urgent need to identify molecular signatures in small cell lung cancer (SCLC) that may select patients who are likely to respond to molecularly targeted therapies. In this study, we investigate the feasibility of undertaking focused molecular analyses on routine diagnostic biopsies in patients with SCLC.

Methods: A series of histopathologically confirmed formalin-fixed, paraffin-embedded SCLC specimens were analysed for epidermal growth factor receptors (EGFR), KRAS, NRAS and BRAF mutations, ALK gene rearrangements and MET amplification. EGFR and KRAS mutation testing was evaluated using real time polymerase chain reaction (RT-PCR cobas®), BRAF and NRAS mutations using multiplex PCR and capillary electrophoresis-single strand conformation analysis, and ALK and MET aberrations with fluorescent in situ hybridization. All genetic aberrations detected were validated independently.

Results: A total of 105 patients diagnosed with SCLC between July 1990 and September 2006 were included. 60 (57 %) patients had suitable tumour tissue for molecular testing. 25 patients were successfully evaluated for all six pre-defined molecular aberrations. Eleven patients failed all molecular analysis. No mutations in EGFR, KRAS and NRAS were detected, and no ALK gene rearrangements or MET gene amplifications were identified. A V600E substitution in BRAF was detected in a Caucasian male smoker diagnosed with SCLC with squamoid and glandular features.

Conclusion: The paucity of patients with sufficient tumour tissue, quality of DNA extracted and low frequency of aberrations detected indicate that alternative molecular characterisation approaches are necessary, such as the use of circulating plasma DNA in patients with SCLC.
Original languageEnglish
Pages (from-to)688
JournalBMC Research Notes
Volume8
Issue number688
DOIs
Publication statusPublished - 18 Nov 2015

Keywords

  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase
  • DNA Mutational Analysis/methods
  • ErbB Receptors/genetics
  • Feasibility Studies
  • Female
  • GTP Phosphohydrolases/genetics
  • Genetic Predisposition to Disease/genetics
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms/diagnosis
  • Male
  • Membrane Proteins/genetics
  • Middle Aged
  • Molecular Diagnostic Techniques/methods
  • Mutation
  • Paraffin Embedding/methods
  • Proto-Oncogene Proteins B-raf/genetics
  • Proto-Oncogene Proteins c-met/genetics
  • Proto-Oncogene Proteins p21(ras)/genetics
  • Receptor Protein-Tyrosine Kinases/genetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Small Cell Lung Carcinoma/diagnosis
  • Tissue Fixation/methods

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  • Cite this

    Abdelraouf, F., Sharp, A., Maurya, M., Mair, D., Wotherspoon, A., Leary, A., Gonzalez de Castro, D., Bhosle, J., Nassef, A., Gaafar, T., Popat, S., Yap, T. A., & O'Brien, M. (2015). Focused molecular analysis of small cell lung cancer: feasibility in routine clinical practice. Feasibility in routine clinical practice. BMC Research Notes, 8(688), 688. https://doi.org/10.1186/s13104-015-1675-x, https://doi.org/10.1186/s13104-015-1675-x