Prevalence and characteristics of TERT and TERC mutations in suspected genetic pulmonary fibrosis

Raphael Borie (1, 2) , L. Tabèze (2, 1) , Gabriel Thabut (3, 1) , Hilario Nunes (4) , Vincent Cottin (5, 6) , Sylvain Marchand-Adam (7) , Grégoire Prevot (8) , Abdellatif Tazi (9) , Jacques Cadranel (10, 11) , Herve Mal (3) , Lidwine Wemeau-Stervinou (12) , Anne Bergeron Lafaurie (9) , Dominique Israel-Biet (13) , Clement Picard (14, 15) , Martine Reynaud Gaubert (16) , Stephane Jouneau (17, 18) , Jean-Marc Naccache (10) , J. Mankikian (7) , Christelle Ménard (19) , Jean-François Cordier (20, 21) , Dominique Valeyre (22) , M. Reocreux (23) , Bernard Grandchamp (24) , Patrick Revy (25) , Caroline Kannengiesser (23) , Bruno Crestani (26, 2, 27, 28)

1 PHERE (UMR_S_1152 / U1152) - Physiopathologie et Epidémiologie des Maladies Respiratoires
2 Service de Pneumologie A
3 Service de pneumologie B
4 Service de médecine nucléaire [Bobigny]
5 Centre de Référence des Maladies Pulmonaires Rares [Hôpital Louis Pradel - HCL]
6 Department of Pneumology [Lyon]
7 Pathologies Respiratoires : Protéolyse et Aérosolthérapie
8 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
9 Service de pneumologie [Saint-Louis]
10 Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon]
11 Theranoscan
12 Service d'oncologie médicale (CHRU Lille)
13 Assistance Publique-Hôpitaux de Paris; Hôpital Européen Georges Pompidou; Service de Pneumologie; Paris
14 EFS - Alpes-Méditerranée - Etablissement Français du Sang - Alpes-Méditerranée
15 ADES - Anthropologie bio-culturelle, Droit, Ethique et Santé
16 CHU Marseille
17 Irset - Institut de recherche en santé, environnement et travail
18 CIC - Centre d'Investigation Clinique [Rennes]
19 MiCa - Microenvironnement et cancer
20 UCBL - Université Claude Bernard Lyon 1
21 Hôpital Louis Pradel [CHU - HCL]
22 Service des maladies respiratoires
23 Hôpital Bichat - Claude Bernard
24 OMMIC S.A.S.
25 Developpement Normal et Pathologique du Système Immunitaire
26 Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire
27 Département Hospitalo-universtaire FIRE (Fibrosis, Inflammation and Remodeling)
28 Service de pneumologie A

Telomerase reverse transcriptase (TERT) or telomerase RNA (TERC) gene mutation is a major monogenic cause of pulmonary fibrosis. Sequencing of TERT/TERC genes is proposed to patients with familial pulmonary fibrosis. Little is known about the possible predictors of this mutation and its impact on prognosis. We retrospectively analysed all the genetic diagnoses made between 2007-2014 in patients with pulmonary fibrosis. We evaluated the prevalence of TERT/TERC disease-Associated variant (DAV), factors associated with a DAV, and the impact of the DAV on survival. 237 patients with pulmonary fibrosis (153 with familial pulmonary fibrosis, 84 with telomere syndrome features without familial pulmonary fibrosis) were tested for TERT/TERC DAV. DAV was diagnosed in 40 patients (16.8%), including five with non-idiopathic interstitial pneumonia. Prevalence of TERT/TERC DAV did not significantly differ between patients with familial pulmonary fibrosis or with only telomere syndrome features (18.2% versus 16.4%). Young age, red blood cell macrocytosis, and low platelet count were associated with the presence of DAV; the probability of DAV was increased for patients 40-60 years. Transplant-free survival was lower with than without TERT/TERC DAV (4.2 versus 7.2 years; p=0.046). TERT/TERC DAV were associated with specific clinical and biological features and reduced transplantfree survival. ©ERS 2016.

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Ecology, environment

Raphael Borie, L. Tabèze, Gabriel Thabut, Hilario Nunes, Vincent Cottin, et al.. Prevalence and characteristics of TERT and TERC mutations in suspected genetic pulmonary fibrosis. European Respiratory Journal, 2016, 48 (6), pp.1721--1731. ⟨10.1183/13993003.02115-2015⟩. ⟨hal-01467555⟩