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Somatic driver mutation pattern in NSCLC varies by race
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Black patients with non–small cell lung cancer exhibited a different pattern of somatic driver mutations than white patients, according to results of a pooled analysis.
“The majority of driver alterations in [black patients] are yet to be described, which will require more comprehensive panels and assessment of noncanonical alterations,” Luiz H. Araujo, MD, MSc, of the department of internal medicine at James Thoracic Center at The Ohio State University Comprehensive Cancer Center, and colleagues wrote.
Araujo and colleagues collected samples from black patients with NSCLC treated between 1998 and 2011 at sites in Tennessee, Ohio and Michigan.
The researchers used SNaPshot or next-generation sequencing to assess gene mutations, and they used fluorescence in situ hybridization to evaluate anaplastic lymphoma kinase (ALK) translocations.
The analysis included samples from 260 patients (median age, 60 years; range, 35-85), the majority of whom were men (62.3%). Two-thirds of the cohort (63.5%) were current smokers and 23.1% were former smokers.
One-third (31.2%) of patients had squamous cell carcinomas. Forty percent of patients had advanced disease (stage III, 15.8%; stage IV, 23.8%).
The most frequently identified mutations were KRAS (15.4%), epidermal growth factor receptor (EGFR, 5%) and PIK3CA (0.8%), followed by BRAF, ERBB2, AKTI and NRAS (0.4% each). Researchers detected ALK translocations in two (1.7%) nonsquamous tumors.
Overall, results showed 61 cases (23.5%) harbored a classic driver alteration, with no overlap among major drivers. About one-third (n = 54; 30.2%) of nonsquamous samples presented a driver alteration.
To compare the frequency of driver mutations between black and white patients, Araujo and colleagues used The Cancer Genome Atlas to identify 283 NSCLC cases resected from white patients (median age, 67 years; 51.2% men; 19.1% advanced disease). Other characteristics between the patient groups were similar.
The frequency of any driver mutation was significantly higher among white patients (31.8% vs. 23.5%; P = .035).
However, the frequency of any KRAS (18% for whites vs. 15.4% for blacks) and EGFR (6% for whites vs. 5% for blacks) did not differ.
Multivariate analysis showed ethnicity was an independent factor associated with any driver mutation, although only two factors — smoking status and histology — were significantly associated with KRAS and EGFR status.
A matching technique that accounted for baseline variables confirmed that the frequency of any driver mutation was consistently lower in black patients, whereas frequency of EGFR and KRAS did not vary significantly.
Among the cohort of black patients, those whose tumors harbored EGFR mutations experienced significantly longer OS (P = .067). Neither KRAS status nor presence of any mutation had a significant effect on survival. – by Jeff Craven
Disclosure: The researchers report no relevant financial disclosures.
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