title: Clinical and epidemiological study of EGFR mutations and EML4-ALK fusion genes among Indian patients with adenocarcinoma of the lung.
abstract: BACKGROUND
  Mutation in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) is a common feature observed in lung adenocarcinoma. A fusion gene between echinoderm microtubule-associated protein-like 4 (EML4) and the intracellular domain of anaplastic lymphoma kinase (ALK), named EML4-ALK, has been identified in a subset of non-small-cell lung cancer (NSCLC) tumors. The objective of this study was to determine the prevalence of EGFR mutations and EML4-ALK fusions in Indian patients with NSCLC (adenocarcinoma) as well as evaluate their clinical characteristics.
  
  
  METHODS
  Patients with NSCLC, adenocarcinoma histology, whose tumors had been tested for EGFR mutational status, were considered for this study. ALK gene rearrangement was detected by fluorescence in situ hybridization using the Vysis ALK Break Apart Rearrangement Probe Kit. ALK mutation was tested in samples that were negative for EGFR mutation.
  
  
  RESULTS
  A total of 500 NSCLC adenocarcinoma patients were enrolled across six centers. There were 337 (67.4%) men and 163 (32.6%) women with a median age of 58 years. One hundred and sixty-four (32.8%) blocks were positive for EGFR mutations, whereas 336 (67.2%) were EGFR wild-type. Of the 336 EGFR-negative blocks, EML4-ALK fusion gene was present in 15 (4.5%) patients, whereas 321 (95.5%) tumors were EML4-ALK negative. The overall incidence of EML4-ALK fusion gene was 3% (15/500).
  
  
  CONCLUSIONS
  The incidence of EGFR mutations (33%) in this Indian population is close to the reported incidence in Asian patients. EML4-ALK gene fusions are present in lung adenocarcinomas from Indian patients, and the 3% incidence of EML4-ALK gene fusion in EGFR mutation-negative cases is similar to what has been observed in other Western and Asian populations. The mutual exclusivity of EML4-ALK and EGFR mutations suggests implementation of biomarker testing for tumors harboring ALK rearrangements in order to identify patients that can benefit from newer targeted therapies.
authors.affiliation: Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India.
authors.forename: Dc
authors.initials: D
authors.lastname: Doval
authors.affiliation: Tata Memorial Hospital, Mumbai, India.
authors.forename: K
authors.initials: K
authors.lastname: Prabhash
authors.affiliation: Bangalore Institute of Oncology, HCG Group, Bengaluru, India.
authors.forename: S
authors.initials: S
authors.lastname: Patil
authors.affiliation: Max Super Speciality Hospital, New Delhi, India.
authors.forename: H
authors.initials: H
authors.lastname: Chaturvedi
authors.affiliation: B. P. Poddar Hospital, Kolkata, India.
authors.forename: C
authors.initials: C
authors.lastname: Goswami
authors.affiliation: Medanta The Medicity, Gurgaon, India.
authors.forename: Ak
authors.initials: A
authors.lastname: Vaid
authors.affiliation: Tata Memorial Hospital, Mumbai, India.
authors.forename: S
authors.initials: S
authors.lastname: Desai
authors.affiliation: Oncquest Laboratories Ltd., New Delhi, India.
authors.forename: S
authors.initials: S
authors.lastname: Dutt
authors.affiliation: Triesta Reference Laboratory, HCG Group, Bengaluru, India.
authors.forename: Vh
authors.initials: V
authors.lastname: Veldore
authors.affiliation: Tata Memorial Hospital, Mumbai, India.
authors.forename: N
authors.initials: N
authors.lastname: Jambhekar
authors.affiliation: Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India.
authors.forename: A
authors.initials: A
authors.lastname: Mehta
authors.affiliation: Triesta Reference Laboratory, HCG Group, Bengaluru, India.
authors.forename: D
authors.initials: D
authors.lastname: Hazarika
authors.affiliation: Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India.
authors.forename: S
authors.initials: S
authors.lastname: Azam
authors.affiliation: Pfizer India Ltd., Mumbai, India.
authors.forename: S
authors.initials: S
authors.lastname: Gawande
authors.affiliation: Catalyst Clinical Services Pvt. Ltd., New Delhi, India.
authors.forename: S
authors.initials: S
authors.lastname: Gupta
keywords: Crizotinib; NSCLC; Vysis ALK Break Apart Rearrangement Probe Kit