lungNENomics - Rare Cancers Genomics

We are currently performing a full molecular characterization of atypical carcinoids and supra-carcinoids (an aggressive group of pulmonary carcinoids that we have recently identified) through a multi-omic integrative analysis (WGS, RNA-seq, and 850k methylation arrays) of 100 primary tumors. The molecular data will be correlated with morphological, epidemiological, and clinical features.

We are also assessing the intra-tumor molecular heterogeneity of pulmonary carcinoids through a multi-omic integrative analysis (WGS, RNA-seq, and 850k methylation arrays) of different tumoral regions in a series of 20 carcinoid patients.

Finally, together with T Dayton (in Clever’s lab) we are trying to depict the mechanisms of a possible progression from low to high-aggressive lung neuroendocrine neoplasms by modeling tumor initiation and progression, using state-of-the-art organoid in vitro models.

PUBLICATIONS

Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids. Alcala N, Leblay N, Gabriel AAG, Mangiante L, Hervas D, Giffon T, Sertier AS, Ferrari A, Derks J, Ghantous A, Delhomme TM, Chabrier A, Cuenin C, Abedi-Ardekani B, Boland A, Olaso R, Meyer V, Altmuller J, Le Calvez-Kelm F, Durand G, Voegele C, Boyault S, Moonen L, Lemaitre N, Lorimier P, Toffart AC, Soltermann A, Clement JH, Saenger J, Field JK, Brevet M, Blanc-Fournier C, Galateau-Salle F, Le Stang N, Russell PA, Wright G, Sozzi G, Pastorino U, Lacomme S, Vignaud JM, Hofman V, Hofman P, Brustugun OT, Lund-Iversen M, Thomas de Montpreville V, Muscarella LA, Graziano P, Popper H, Stojsic J, Deleuze JF, Herceg Z, Viari A, Nuernberg P, Pelosi G, Dingemans AMC, Milione M, Roz L, Brcic L, Volante M, Papotti MG, Caux C, Sandoval J, Hernandez-Vargas H, Brambilla E, Speel EJM, Girard N, Lantuejoul S, McKay JD, Foll M, Fernandez-Cuesta L. Nat Commun. 2019 PMID: 31431620. IARC Press Release

A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Rindi G, Klimstra DS, Abedi-Ardekani B, Asa SL, Bosman FT, Brambilla E, Busam KJ, de Krijger RR, Dietel M, El-Naggar AK, Fernandez-Cuesta L, Klöppel G, McCluggage WG, Moch H, Ohgaki H, Rakha EA, Reed NS, Rous BA, Sasano H, Scarpa A, Scoazec JY, Travis WD, Tallini G, Trouillas J, van Krieken JH, Cree IA. Mod Pathol. 2018 PMID: 30140036

Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors. George J, Walter V, Peifer M, Alexandrov LB, Seidel D, Leenders F, Maas L, Müller C, Dahmen I, Delhomme TM, Ardin M, Leblay N, Byrnes G, Sun R, De Reynies A, McLeer-Florin A, Bosco G, Malchers F, Menon R, Altmüller J, Becker C, Nürnberg P, Achter V, Lang U, Schneider PM, Bogus M, Soloway MG, Wilkerson MD, Cun Y, McKay JD, Moro-Sibilot D, Brambilla CG, Lantuejoul S, Lemaitre N, Soltermann A, Weder W, Tischler V, Brustugun OT, Lund-Iversen M, Helland Å, Solberg S, Ansén S, Wright G, Solomon B, Roz L, Pastorino U, Petersen I, Clement JH, Sänger J, Wolf J, Vingron M, Zander T, Perner S, Travis WD, Haas SA, Olivier M, Foll M, Büttner R, Hayes DN, Brambilla E, Fernandez-Cuesta L, Thomas RK. Nat Commun. 2018 PMID: 29535388. 

New insights into the molecular characteristics of pulmonary carcinoids and large cell neuroendocrine carcinomas, and the impact on their clinical management. Derks JL, Leblay N, Lantuejoul S, Dingemans AC, Speel EM, Fernandez-Cuesta L. J Thorac Oncol. 2018 Review. Erratum in: J Thorac Oncol. 2018 Aug;13(8):1229. PMID: 29454048

Molecular subtypes of pulmonary large-cell neuroendocrine carcinoma predict chemotherapy treatment outcome. Derks JL, Leblay N, Thunnissen E, van Suylen RJ, den Bakker M, Groen HJM, Smit EF, Damhuis R, van den Broek EC, Charbrier A, Foll M, McKay JD, Fernandez-Cuesta L, Speel EM, Dingemans AC; PALGA-Group. Clin Cancer Res. 2018 PMID: 29066508

Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids. Fernandez-Cuesta L, Peifer M, Lu X, Sun R, Ozretić L, Seidal D, Zander T, Leenders F, George J, Müller C, Dahmen I, Pinther B, Bosco G, Konrad K, Altmüller J, Nürnberg P, Achter V, Lang U, Schneider PM, Bogus M, Soltermann A, Brustugun OT, Helland Å, Solberg S, Lund-Iversen M, Ansén S, Stoelben E, Wright GM, Russell P, Wainer Z, Solomon B, Field JK, Hyde R, Davies MP, Heukamp LC, Petersen I, Perner S, Lovly C, Cappuzzo F, Travis WD, Wolf J, Vingron M, Brambilla E, Haas SA, Buettner R, Thomas RK. Nat Commun. 2014 PMID: 24670920

Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Peifer M, Fernández-Cuesta L, Sos ML, George J, Seidel D, Kasper LH, Plenker D, Leenders F, Sun R, Zander T, Menon R, Koker M, Dahmen I, Müller C, Di Cerbo V, Schildhaus HU, Altmüller J, Baessmann I, Becker C, de Wilde B, Vandesompele J, Böhm D, Ansén S, Gabler F, Wilkening I, Heynck S, Heuckmann JM, Lu X, Carter SL, Cibulskis K, Banerji S, Getz G, Park KS, Rauh D, Grütter C, Fischer M, Pasqualucci L, Wright G, Wainer Z, Russell P, Petersen I, Chen Y, Stoelben E, Ludwig C, Schnabel P, Hoffmann H, Muley T, Brockmann M, Engel-Riedel W, Muscarella LA, Fazio VM, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman DA, Snijders PJ, Cappuzzo F, Ligorio C, Damiani S, Field J, Solberg S, Brustugun OT, Lund-Iversen M, Sänger J, Clement JH, Soltermann A, Moch H, Weder W, Solomon B, Soria JC, Validire P, Besse B, Brambilla E, Brambilla C, Lantuejoul S, Lorimier P, Schneider PM, Hallek M, Pao W, Meyerson M, Sage J, Shendure J, Schneider R, Büttner R, Wolf J, Nürnberg P, Perner S, Heukamp LC, Brindle PK, Haas S, Thomas RK. Nat Genet. 2012 PMID: 22941188

OTHER SCIENTIFIC COMMUNICATIONS

Nicolas Alcala gave an oral presentation entitled « A multi-disciplinary multi-omics study of spatial and temporal tumor evolution in thoracic cancers with clinical implications » in the 2019 Gilles Thomas' Symposium – October 2-4, 2019 in Lyons (France)

Aurelie Gabriel presented a poster entitled « Integrative and comparative genomic analyses identify clinically-relevant groups of pulmonary carcinoids and unveil the existence of supra-carcinoids » in the 4th International Cancer Symposium of the Cancer Research Center of Lyons – October 2-4, 2019 in Lyons (France)

Nicolas Alcala presented a poster entitled « Exploring spatial and temporal tumor evolution in thoracic cancers using integrative multi-omic analyses » in the EMBO | EMBL Symposium: Multiomics to Mechanisms – Challenges in Data Integration – September 11-13, 2019 in Heidelberg (Germany)

Nicolas Alcala gave an oral presentation entitled « New insights from lung NEN molecular data: new entities or new concepts » in the 31st European Congress of Pathology – September 7-11, 2019 in Nice (France)

Lynnette Fernandez-Cuesta gave an oral presentation entitled « Integrative and comparative genomic analyses identify clinically-relevant groups of pulmonary carcinoids and unveil the existence of supra-carcinoids » in XV International Symposium GETNE 2019 – September 19–20, 2019 in Oviedo (Spain)

Matthieu Foll gave an oral presentation entitled « A multidisciplinary multi-omics study of spatial and temporal tumor evolution in thoracic cancers with clinical implications » in the World Conference on Lung Cancer – September 7–10, 2019 in Barcelona (Spain)

Lynnette Fernandez-Cuesta gave an oral presentation entitled « Machine learning and integrative multi-omics analysis identify novel molecular groups of lung neuroendocrine tumors » in the World Conference on Lung Cancer – September 7–10, 2019 in Barcelona (Spain)

Nicolas Alcala presented a poster entitled « Integrative and comparative genomic analyses identify clinically-relevant groups of pulmonary carcinoids and unveil the existence of supra-carcinoids » in the CLARA 2019 Cancer Research Forum – April 4-5, 2019 in Lyon (France)

Lynnette Fernandez-Cuesta gave an oral presentation entitled « Integrative and comparative genomic analyses identify clinically relevant groups of pulmonary carcinoids and unveil the existence of supra-carcinoids » in the 16th Annual ENETS Conference – March 6-8, 2018 in Barcelona (Spain)

Lynnette Fernandez-Cuesta gave an oral presentation entitled « New insights in molecular pathology of neuroendocrine lung tumours » in the 11th Joint Meeting of the British Division of the IAP and the Pathological Society, together with the NVvP, The Dutch Pathological Society – June 19-22, 2018 in Maastricht (The Netherlands)

FUNDING

Comprehensive molecular characterisation of lung supra-carcinoids. Neuroendocrine Tumor Research Foundation (NETRF, US). 2019 Investigator Award. Active.

Genomic characterisation of broncho-pulmonary carcinoids. Institut National Du Cancer (INCa, France). PRT-K17-047. Coordinators. Active.

The Orthopedia Homeobox transcription factor (OTP) in the diagnostics and tumorigenesis of lung carcinoids. KWF Kankerbestrijding (DCS, The Netherlands). Collaborators. Active.

Epigenomic characterisation of lung neuroendocrine tumours. Ligue Contre le Cancer (LNCC, France). Coordinators. Completed.

Genomic and transcriptomic characterisation of atypical carcinoids of the lung. National Institutes of Health (NIH, US). R03 CA195253-01. Coordinators. Completed.