ALK gene rearrangements in unselected caucasians with non-small cell lung carcinoma (NSCLC).
2010; Lippincott Williams & Wilkins; Volume: 28; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2010.28.15_suppl.10533
ISSN1527-7755
AutoresMarileila Varella‐Garcia, Y. Cho, Xiaojun Lu, Alan Baron, Luigi Terracciano, D. Ross Camidge, P. A. Bunn, Wilbur A. Franklin, Federico Cappuzzo, Robert C. Doebele,
Tópico(s)Colorectal Cancer Treatments and Studies
Resumo10533 Background: Transforming rearrangements of the ALK gene have been reported in a subset of NSCLC, commonly fusing the ALK kinase domain with EML4 promoter but rarer fusion partners (TFG and KIF5B) have also been described. ALK is a valid clinical target based on phase I clinical data with dual ALK/MET inhibitor. We investigated the cytogenetic patterns of ALK rearrangements using FISH and the molecular and clinical characteristics associated with ALK+ in an unselected NSCLC population. Methods: Cohort included 447 NSCLC with previous EGFR and MET copy number gain (CNG) available; median age at diagnosis = 66 years, 83% male, 52% former and 35% current smokers; 52% of tumors were adenocarcinoma/BAC, stage I to IV was 37%, 22%, 27%, and 14%, respectively. Dual color FISH analyses were performed with ALK break-apart probe (Abbott Molecular) and 3 novel fusion probe sets specific for EML4-ALK, KIF5B-ALK and TFG-ALK. Results: Using the break apart probe, 12 patients (2.68%) were identified as ALK+. Multiple different cytogenetic patterns were observed, but virtually all carried the EML4-ALK fusion when specific probe sets were used. Using logistic regression analyses, higher odds were verified for ALK+ among males vs. females (p = 0.03), never vs. ever smokers (p = 0.005), adenocarcinoma vs. other histologies (p = 0.0013), and younger vs. older age (p = 0.08). No association was found between ALK+ and clinical stage, EGFR or MET CNG. There was no association between survival and ALK+ after adjusting for patient's gender, smoking history, histology and age (HR = 0.70; 95% CI 0.0256, 1.913, p = 0.48). Conclusions: In this large study of unselected Caucasian NSCLC patients, ALK+ was associated with male gender, never smoking status and adenocarcinoma histology suggesting these factors could be used to enrich ALK screened populations. The specific FISH probe sets identified EML4- ALK in different FISH patterns observed with the ALK rearrangement probe. ALK+ is distinct from EGFR and MET CNG, suggesting independent molecular mechanisms. ALK+ showed no significant prognostic impact, the observed favorable effect was unstable most likely due to the low number of ALK+. No significant financial relationships to disclose.
Referência(s)