NF1 mutations identify molecular and clinical subtypes of lung adenocarcinomas
Abstract 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 p...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-08-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.2175 |
| _version_ | 1818585011776913408 |
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| author | Camille Tlemsani Nicolas Pécuchet Aurelia Gruber Ingrid Laurendeau Claire Danel Marc Riquet Françoise Le Pimpec‐Barthes Elizabeth Fabre Audrey Mansuet‐Lupo Diane Damotte Marco Alifano Armelle Luscan Benoit Rousseau Dominique Vidaud Jennifer Varin Beatrice Parfait Ivan Bieche Karen Leroy Pierre Laurent‐Puig Benoit Terris Helene Blons Michel Vidaud Eric Pasmant |
| author_facet | Camille Tlemsani Nicolas Pécuchet Aurelia Gruber Ingrid Laurendeau Claire Danel Marc Riquet Françoise Le Pimpec‐Barthes Elizabeth Fabre Audrey Mansuet‐Lupo Diane Damotte Marco Alifano Armelle Luscan Benoit Rousseau Dominique Vidaud Jennifer Varin Beatrice Parfait Ivan Bieche Karen Leroy Pierre Laurent‐Puig Benoit Terris Helene Blons Michel Vidaud Eric Pasmant |
| author_sort | Camille Tlemsani |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-16T08:30:17Z |
| format | Article |
| id | doaj.art-1a977a17d1364953847cb9500545d65d |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-16T08:30:17Z |
| publishDate | 2019-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-1a977a17d1364953847cb9500545d65d2022-12-21T22:37:53ZengWileyCancer Medicine2045-76342019-08-01894330433710.1002/cam4.2175NF1 mutations identify molecular and clinical subtypes of lung adenocarcinomasCamille Tlemsani0Nicolas Pécuchet1Aurelia Gruber2Ingrid Laurendeau3Claire Danel4Marc Riquet5Françoise Le Pimpec‐Barthes6Elizabeth Fabre7Audrey Mansuet‐Lupo8Diane Damotte9Marco Alifano10Armelle Luscan11Benoit Rousseau12Dominique Vidaud13Jennifer Varin14Beatrice Parfait15Ivan Bieche16Karen Leroy17Pierre Laurent‐Puig18Benoit Terris19Helene Blons20Michel Vidaud21Eric Pasmant22Service de Génétique et Biologie Moléculaires, Hôpital Cochin, Hôpitaux Universitaires Paris Centre Assistance Publique‐Hôpitaux de Paris (AP‐HP) Paris FranceINSERM UMR‐S1147 Université Sorbonne‐Paris‐Cité Paris FranceEA7331, Faculté de Pharmacie de Paris Université Paris Descartes Paris FranceEA7331, Faculté de Pharmacie de Paris Université Paris Descartes Paris FranceService d'Anatomopathologie Hôpital Bichat, AP‐HP Paris FranceService de Chirurgie Thoracique Hôpital Européen Georges Pompidou (HEGP), AP‐HP Paris FranceService de Chirurgie Thoracique Hôpital Européen Georges Pompidou (HEGP), AP‐HP Paris FranceINSERM UMR‐S1147 Université Sorbonne‐Paris‐Cité Paris FranceService d'Anatomopathologie Hôpital Cochin, Hôpitaux Universitaires Paris Centre, AP‐HP Paris FranceService d'Anatomopathologie Hôpital Cochin, Hôpitaux Universitaires Paris Centre, AP‐HP Paris FranceService de Chirurgie Thoracique Hôpital Cochin, Hôpitaux Universitaires Paris Centre, AP‐HP Paris FranceService de Génétique et Biologie Moléculaires, Hôpital Cochin, Hôpitaux Universitaires Paris Centre Assistance Publique‐Hôpitaux de Paris (AP‐HP) Paris FranceService d'Oncologie Médicale hôpital Henri‐Mondor, AP‐HP Créteil FranceService de Génétique et Biologie Moléculaires, Hôpital Cochin, Hôpitaux Universitaires Paris Centre Assistance Publique‐Hôpitaux de Paris (AP‐HP) Paris FranceEA7331, Faculté de Pharmacie de Paris Université Paris Descartes Paris FranceService de Génétique et Biologie Moléculaires, Hôpital Cochin, Hôpitaux Universitaires Paris Centre Assistance Publique‐Hôpitaux de Paris (AP‐HP) Paris FranceEA7331, Faculté de Pharmacie de Paris Université Paris Descartes Paris FranceService de Génétique et Biologie Moléculaires, Hôpital Cochin, Hôpitaux Universitaires Paris Centre Assistance Publique‐Hôpitaux de Paris (AP‐HP) Paris FranceINSERM UMR‐S1147 Université Sorbonne‐Paris‐Cité Paris FranceService d'Anatomopathologie Hôpital Cochin, Hôpitaux Universitaires Paris Centre, AP‐HP Paris FranceINSERM UMR‐S1147 Université Sorbonne‐Paris‐Cité Paris FranceService de Génétique et Biologie Moléculaires, Hôpital Cochin, Hôpitaux Universitaires Paris Centre Assistance Publique‐Hôpitaux de Paris (AP‐HP) Paris FranceService de Génétique et Biologie Moléculaires, Hôpital Cochin, Hôpitaux Universitaires Paris Centre Assistance Publique‐Hôpitaux de Paris (AP‐HP) Paris FranceAbstract 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.https://doi.org/10.1002/cam4.2175lung adenocarcinomamolecular subtypenext generation sequencingNF1RAS‐MAPK pathway |
| spellingShingle | Camille Tlemsani Nicolas Pécuchet Aurelia Gruber Ingrid Laurendeau Claire Danel Marc Riquet Françoise Le Pimpec‐Barthes Elizabeth Fabre Audrey Mansuet‐Lupo Diane Damotte Marco Alifano Armelle Luscan Benoit Rousseau Dominique Vidaud Jennifer Varin Beatrice Parfait Ivan Bieche Karen Leroy Pierre Laurent‐Puig Benoit Terris Helene Blons Michel Vidaud Eric Pasmant NF1 mutations identify molecular and clinical subtypes of lung adenocarcinomas Cancer Medicine lung adenocarcinoma molecular subtype next generation sequencing NF1 RAS‐MAPK pathway |
| title | NF1 mutations identify molecular and clinical subtypes of lung adenocarcinomas |
| title_full | NF1 mutations identify molecular and clinical subtypes of lung adenocarcinomas |
| title_fullStr | NF1 mutations identify molecular and clinical subtypes of lung adenocarcinomas |
| title_full_unstemmed | NF1 mutations identify molecular and clinical subtypes of lung adenocarcinomas |
| title_short | NF1 mutations identify molecular and clinical subtypes of lung adenocarcinomas |
| title_sort | nf1 mutations identify molecular and clinical subtypes of lung adenocarcinomas |
| topic | lung adenocarcinoma molecular subtype next generation sequencing NF1 RAS‐MAPK pathway |
| url | https://doi.org/10.1002/cam4.2175 |
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