NRG1 fusion in a French cohort of invasive mucinous lung adenocarcinoma

• Published in: Cancer medicine (Malden, MA) MA), 2016-12, Vol.5 (12), p.3579-3585
• Main Authors: Duruisseaux, Michaël, McLeer‐Florin, Anne, Antoine, Martine, Alavizadeh, Sanaz, Poulot, Virginie, Lacave, Roger, Rabbe, Nathalie, Cadranel, Jacques, Wislez, Marie
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Adenocarcinoma, Mucinous - genetics; Adenocarcinoma, Mucinous - pathology; Aged; Aged, 80 and over; Biomarkers, Tumor; Cancer; Cancer Biology; Cancer therapies; Cloning; Cohort Studies; Deoxyribonucleic acid; DNA; Epidermal growth factor receptors; ErbB-2 protein; Ethnicity; Female; FISH; Human health and pathology; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; invasive mucinous adenocarcinoma; Invasiveness; Life Sciences; lung adenocarcinoma; Lung cancer; Lung diseases; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Middle Aged; Minority & ethnic groups; molecular oncology; Mutation; Neoplasm Invasiveness; Neuregulin-1 - genetics; Neuregulin-1 - metabolism; NRG1; Oncogene Proteins, Fusion - genetics; Oncogene Proteins, Fusion - metabolism; Pulmonology and respiratory tract; Short Report; Studies; Therapeutic applications; Tumors
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.838

Invasive mucinous lung adenocarcinoma (IMA) is a rare subtype of lung adenocarcinoma with no effective treatment option in advanced disease. KRAS mutations occur in 28–87% of the cases. NRG1 fusions were recently discovered in KRAS‐negative IMA cases and otherwise negative for known driver oncogenes and could represent an attractive therapeutic target. Published data suggest that NRG1 fusions occur essentially in nonsmoking Asian women. From an IMA cohort of 25 French patients of known ethnicity, driver oncogenes EGFR, KRAS, BRAF, ERBB2 mutations, and ALK and ROS1 rearrangements presence were analyzed. In the IMA samples remaining negative for these driver oncogenes, an NRG1 rearrangement detection was performed by FISH. A driver oncogene was identified in 14/25 IMA, namely 12 KRAS mutations (48%), one ROS1 rearrangement (4%), and one ALK rearrangement (4%). The detection of NRG1 rearrangement by FISH was conducted in the 11 pan‐negative IMA. One sample was NRG1FISH‐positive and 100% of the tumor nuclei analyzed were positive. This NRG1‐positive patient was a 61‐year‐old nonsmoking woman of Vietnamese ethnicity and was the sole patient of Asian ethnicity of the cohort. She died 6 months after the diagnosis with a pulmonary multifocal disease. NRG1FISH detection should be considered in patients with IMA pan‐negative for known driver oncogenes. These results might suggest that NRG1 fusion is more frequent in IMA from Asian patient. Larger studies are needed. NRG1 fusions may represent a therapeutic target in advanced invasive mucinous adenocarcinomas (IMA) pan‐negative for driver oncogenes. Among a French cohort of 25 IMA, we identified 11 pan‐negative IMA, one of which was NRG1 FISH‐positive. The NRG1‐positive patient was the sole of Asian ethnicity. NRG1 FISH testing should be considered in pan‐negative IMA, and in particular in Asian patients.