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01.12.2019 | Research article | Ausgabe 1/2019 Open Access

BMC Pulmonary Medicine 1/2019

EGFR, KRAS, BRAF, ALK, and cMET genetic alterations in 1440 Sardinian patients with lung adenocarcinoma

BMC Pulmonary Medicine > Ausgabe 1/2019
Maria Colombino, Panagiotis Paliogiannis, Antonio Cossu, Davide Adriano Santeufemia, Maria Cristina Sini, Milena Casula, Grazia Palomba, Antonella Manca, Marina Pisano, Valentina Doneddu, Giuseppe Palmieri, Sardinian Lung Cancer (SLC) Study Group
Wichtige Hinweise
Maria Colombino, Panagiotis Paliogiannis and Antonio Cossu contributed equally to this work.

Supplementary information

Supplementary information accompanies this paper at https://​doi.​org/​10.​1186/​s12890-019-0964-x.

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Lung cancer is one of the most incident neoplastic diseases, and a leading cause of death for cancer worldwide. Knowledge of the incidence of druggable genetic alterations, their correlation with clinical and pathological features of the disease, and their interplay in cases of co-occurrence is crucial for selecting the best therapeutic strategies of patients with non-small cell lung cancer. In this real-life study, we describe the molecular epidemiology of genetic alterations in five driver genes and their correlations with the demographic and clinical characteristics of Sardinian patients with lung adenocarcinoma.


Data from 1440 consecutive Sardinian patients with a histologically proven diagnosis of lung adenocarcinoma from January 2011 through July 2016 were prospectively investigated. EGFR mutation analysis was performed for all of them, while KRAS and BRAF mutations were searched in 1047 cases; ALK alterations were determined with fluorescence in situ hybridization in 899 cases, and cMET amplifications in 788 cases.


KRAS mutations were the most common genetic alterations involving 22.1% of the cases and being mutually exclusive with the EGFR mutations, which were found in 12.6% of them. BRAF mutations, ALK rearrangements, and cMET amplifications were detected in 3.2, 5.3, and 2.1% of the cases, respectively. Concomitant mutations were detected only in a few cases.


Almost all the genetic alterations studied showed a similar incidence in comparison with other Caucasian populations. Concomitant mutations were rare, and they probably have a scarce impact on the clinical management of Sardinians with lung adenocarcinoma. The low incidence of concomitant cMET amplifications at diagnosis suggests that these alterations are acquired in subsequent phases of the disease, often during treatment with TKIs.
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