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Mutational profile of Brazilian lung adenocarcinoma unveils association of EGFR mutations with high Asian ancestry and independent prognostic role of KRAS mutations

2019; Nature Portfolio; Volume: 9; Issue: 1 Linguagem: Inglês

10.1038/s41598-019-39965-x

2045-2322

Letícia Ferro Leal, Flávia Escremim de Paula, Pedro De Marchi, Luciano de Souza Viana, Gustavo Dix Junqueira Pinto, Carolina Dias Carlos, Gustavo Nóriz Berardinelli, José Elias Miziara, Carlos Maciel da Silva, Eduardo Caetano Albino da Silva, Rui Pereira, Marco Antônio de Oliveira, Cristovam Scapulatempo‐Neto, Rui Manuel Reis,

Lung Cancer Research Studies

Abstract Lung cancer is the deadliest cancer worldwide. The mutational frequency of EGFR and KRAS genes in lung adenocarcinoma varies worldwide per ethnicity and smoking. The impact of EGFR and KRAS mutations in Brazilian lung cancer remains poorly explored. Thus, we investigated the frequency of EGFR and KRAS mutations in a large Brazilian series of lung adenocarcinoma together with patients’ genetic ancestry, clinicopathological and sociodemographic characteristics. The mutational frequency of EGFR was 22.7% and KRAS was 20.4%. The average ancestry proportions were 73.1% for EUR, 13.1% for AFR, 6.5% for AME and 7.3% for ASN. EGFR mutations were independently associated with never-smokers, high-Asian ancestry, and better performance status. KRAS mutations were independently associated with tobacco exposure and non-Asian ancestry. EGFR -exon 20 mutations were associated with worse outcome. The Cox regression model indicated a worse outcome for patients whose were older at diagnosis (>61 y), solid histological subtype, loss of weight (>10%), worse performance status (≥2), and presence of KRAS mutations and EGFR mutational status in TKi non-treated patients. In conclusion, we assessed the clinicopathological and ethnic impact of EGFR and KRAS mutations in the largest series reported of Brazilian lung adenocarcinomas. These findings can support future clinical strategies for Brazilian lung cancer patients.