Open AccessNF1 mutations identify molecular and clinical subtypes of lung adenocarcinomas
Author(s) -
Tlemsani Camille,
Pécuchet Nicolas,
Gruber Aurelia,
Laurendeau Ingrid,
Danel Claire,
Riquet Marc,
Le PimpecBarthes Françoise,
Fabre Elizabeth,
MansuetLupo Audrey,
Damotte Diane,
Alifano Marco,
Luscan Armelle,
Rousseau Benoit,
Vidaud Dominique,
Varin Jennifer,
Parfait Beatrice,
Bieche Ivan,
Leroy Karen,
LaurentPuig Pierre,
Terris Benoit,
Blons Helene,
Vidaud Michel,
Pasmant Eric
Publication year - 2019
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2175
Subject(s) - kras , adenocarcinoma , lung cancer , cancer research , carcinogenesis , oncology , medicine , ros1 , biology , mutation , gene , cancer , genetics
The tumor suppressor gene neurofibromin 1 ( NF1 ) is a major regulator of the RAS‐MAPK pathway. NF1 mutations occur in lung cancer but were not extensively explored. We hypothesized that NF1 ‐mutated tumors could define a specific population with a distinct clinical and molecular profile. We performed NF1 sequencing using next generation sequencing (NGS) in 154 lung adenocarcinoma surgical specimens with known KRAS , EGFR , TP53 , BRAF , HER2 , and PIK3CA status, to evaluate the molecular and clinical specificities of NF1 ‐mutated lung cancers. Clinical data were retrospectively collected, and their associations with molecular profiles assessed. In this series, 24 tumors were NF1 mutated (17.5%) and 11 were NF1 deleted (8%). There was no mutation hotspot. NF1 mutations were rarely associated with other RAS‐MAPK pathway mutations. Most of patients with NF1 alterations were males (74.3%) and smokers (74.3%). Overall survival and disease‐free survival were statistically better in patients with NF1 alterations (N = 34) than in patients with KRAS mutations (N = 30) in univariate analysis. Our results confirm that NF1 is frequently mutated and represents a distinct molecular and clinical subtype of lung adenocarcinoma.