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The Clinical and Molecular Profile of ALK in NSCLC

The Clinical and Molecular Profile of ALK in NSCLC

A number of studies have examined clinical or demographic factors associated with EML4-ALK gene rearrangements. Compared with patients who have ALK-negative disease, factors associated with ALK-positive NSCLC are:

  • Younger median age (<60 years)1-5
  • Non-smoking or light smoking history1-5,7
  • Adenocarcinoma or mixed histology1,3-7
  • A solid growth pattern with signet-ring cells2,3

Data have suggested that tumours with EML4-ALK gene rearrangements generally do not have mutations in the genes for epidermal growth factor receptor (EGFR)1-4,6,7 or V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue (KRAS).3-7 However, cases of NSCLC with EGFR mutations or KRAS mutations and concomitant EML4-ALK rearrangements have also been reported.5,8,9

Despite the correlations between these clinical or histological features and ALK status, it is possible for any patient with NSCLC to have ALK-positive disease. For example, the EML4-ALK fusion gene has been found in older patients with a smoking history.2 This suggests that clinical characteristics alone cannot detect all patients and that molecular testing is essential to determine ALK status.

Currently, the exact prevalence of EML4-ALK in NSCLC is unknown (see table below), but it has been estimated that between 3% and 5% of North American patients with NSCLC have this genetic inversion.10 Data vary between studies because of differences in patient selection criteria and EML4-ALK detection methods.11

Study Nationality of patients with NSCLC No. with
Percent with 
Analytic method
Soda et al. 200712 Japanese 5/75 6.7% RT-PCR
Inamura et al. 200813 Japanese 5/221 2.2% RT-PCR
Takeuchi et al. 200814 Japanese 11/364 3.0% RT-PCR
Perner et al. 200815 Swiss and US 16/603 2.7% FISH, RT-PCR
Koivunen et al. 200816 Korean and US 8/305 2.6% RT-PCR
Korean 6/167 3.6%
US 2/138 1.4%
Shinmura et al. 200817 Japanese 2/77 2.6% RT-PCR
Rodig et al. 20092 US 20/358 5.6% FISH
Martelli et al. 20098 Italian and Spanish 9/120 7.5% RT-PCR
Wong et al. 20094 Chinese 13/266 4.9% RT-PCR
Shaw et al. 20093 US* 19/141 13.5% FISH
Boland et al. 20096 US 6/335 1.8% FISH, RT-PCR
Sakairi et al. 20101 Japanese 7/109 6.4% FISH, RT-PCR
Takahashi et al. 20107 Japanese 5/313 1.6% RT-PCR
Zhang et al. 20105 Chinese 12/103 11.6% RACE-coupled PCR sequencing
Salido et al. 201118 Spanish 2/107 1.9% FISH
Prevalence of EML4-ALK gene rearrangements in various studies

*These patients were selected for genetic screening because of their higher risk of EML4-ALK based on clinical/demographic characteristics.

FISH: fluorescence in-situ hybridisation
RACE: rapid amplification of cDNA ends
RT-PCR: reverse transcription-polymerase chain reaction



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