title: Mutational profiling of bone metastases from lung adenocarcinoma: results of a prospective study (POUMOS-TEC).
abstract: Targeted therapies have improved patient survival in metastatic lung adenocarcinoma. Molecular diagnosis is a key element to identify oncogenic drivers predicting the efficacy of these agents. In stage IV patients, histopathological diagnosis is often performed on bone metastases biopsy, but routine procedure of decalcification may alter DNA quality for subsequent molecular tests. We set up a procedure to perform molecular analyses on bone metastasis and describe the results of mutational profiling. POUMOS-TEC is a prospective study conducted in stage IV lung adenocarcinomas. Bone metastasis specimens from surgery and CT-scan guided biopsies were sent fresh for immediate formalin-fixation. Decalcification was performed, only when necessary, using EDTA. Controls were processed with acid decalcification. DNA extraction was performed after laser microdissection. Mutational profiling of oncogenic drivers was conducted as recommended by the French National Cancer Institute. Diagnosis efficiency of the computed tomography (CT)-scan guided biopsy process was assessed. Among 177 collected bone metastases specimens, 49 came from lung adenocarcinomas. Specimens processed with no decalcification or EDTA (n=45) provided high-quality DNA. Molecular profiling was performed in 44/45 (98%) of cases. The results of the whole panel of oncogenic drivers (EGFR, KRAS, BRAF, PIK3CA, HER2 and ALK) were obtained in 41/45 (91%) of cases. A mutation was observed in 50% of cases including 32% of KRAS and 14% of epidermal growth factor receptor (EGFR) mutations. CT-scan biopsy efficiency rate was 96%. We demonstrated the feasibility to routinely conduct mutational profiling on bone metastases biopsies. We observed a higher rate of EGFR mutations (+42%) in comparison with the average rate of all stage IV lung adenocarcinomas. This procedure is a new step toward the goal of personalized medicine to treat lung cancers and other osteophilic tumors.
authors.affiliation: Inserm UMR1033-Université de Lyon , Lyon, France ; Rheumatology Department, Hôpital Edouard Herriot, Hospices Civils de Lyon , Lyon, France.
authors.forename: Cyrille B
authors.initials: CB
authors.lastname: Confavreux
authors.affiliation: Respiratory Medicine, Thoracic Oncology Department, Hôpital Louis Pradel, Hospices Civils de Lyon , Lyon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Girard
authors.affiliation: Inserm UMR1033-Université de Lyon , Lyon, France ; Radiology Department, Hôpital Edouard Herriot, Hospices Civils de Lyon , Lyon, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Pialat
authors.affiliation: Pathology Department, Molecular Diagnostics Platform, Hôpital Edouard Herriot, Hospices Civils de Lyon , Lyon, France ; Cancer Research Center of Lyon (CRCL) , Lyon, France.
authors.forename: Pierre-Paul
authors.initials: PP
authors.lastname: Bringuier
authors.affiliation: Cancer Research Center of Lyon (CRCL) , Lyon, France ; Pathology Department, Hôpital de la Croix Rousse, Hospices Civils de Lyon , Lyon, France.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Devouassoux-Shisheboran
authors.affiliation: Inserm UMR1033-Université de Lyon , Lyon, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Rousseau
authors.affiliation: Pathology Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon , Lyon, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Isaac
authors.affiliation: Pathology Department, Groupement Hospitalier Est, Hospices Civils de Lyon , Lyon, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Thivolet-Bejui
authors.affiliation: Inserm UMR1033-Université de Lyon , Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Clezardin
authors.affiliation: Inserm UMR1033-Université de Lyon , Lyon, France ; Pathology Department, Groupement Hospitalier Est, Hospices Civils de Lyon , Lyon, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Brevet