title: Primary lung adenocarcinoma occurring in a PTEN related syndrome (Cowden's disease): routine EGFR sequencing also highlights two rare somatic mutations S768I and V769L.
abstract: Cowden's syndrome is a rare autosomal dominant disorder that has been linked to germline mutations in the phosphatase and TENsin homolog (PTEN) gene. PTEN is a tumour suppressor gene that negatively regulates the PI3K-AKT-mTOR pathway. Cowden's syndrome is a multi-system disease with increased risks for a number of malignancies but very rarely for lung cancer. A systematic follow-up chest CT scan was performed to a 42 year's old female, light smoker. It showed a 20mm opacity of the left upper pulmonary lobe. Differential diagnose with benign tumours (such as hamartoma) was carefully searched. Procedures led to the diagnosis of a primitive lung adenocarcinoma. EGFR sequencing shows two rare somatic mutations (S768I and V769L). Lack of expression of PTEN is a non-sufficient condition leads to lung cancer formation alone. Nevertheless, it increases cell oncogenic potential. PTEN lacking in non small cell lung cancer is a frequent issue. It could be an alternative mechanism of non-efficacy of EGFR-TKI in cells with a sensitizing EGFR mutation. This case report, a very rare entity: a patient with a PTEN germline mutation and a lung adenocarcinoma harbouring two concomitant rare somatic mutations of EGFR. This observation comforts PTENs role in lung oncogenesis.
authors.affiliation: Service de pneumologie et oncologie thoracique, Hospices Civils de Lyon, CH Lyon Sud, 165 chemin du Grand Revoyet, Pierre Bénite Cédex, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Boespflug
authors.forename: Sébastien
authors.initials: S
authors.lastname: Couraud
authors.forename: Pierre-Paul
authors.initials: PP
authors.lastname: Bringuier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Isaac
authors.forename: Laurence
authors.initials: L
authors.lastname: Gérinière
authors.forename: Emilie
authors.initials: E
authors.lastname: Perrot
authors.forename: Patrick
authors.initials: P
authors.lastname: Edery
authors.forename: Isabelle
authors.initials: I
authors.lastname: Durieu
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Souquet
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000235:genetics*; D000328:Adult; D025063:Chromosome Disorders / Q000235:genetics; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006223:Hamartoma Syndrome, Multiple / Q000150:complications / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012694:Serine / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014633:Valine / Q000235:genetics
chemical_list: D012694:Serine; D019869:Phosphatidylinositol 3-Kinases; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; D014633:Valine