Synchronous primary lung adenocarcinomas harboring distinct MET Exon 14 splice site mutations. (August 2018)

• Record Type: Journal Article
• Authors: Wang, Samantha X.Y.; Lei, Li; Guo, Haiwei H.; Shrager, Joseph; Kunder, Christian A.; Neal, Joel W.
• Is Part Of: Lung cancer. Volume 122(2018)
• Page Start: 187
• Page End: 191
• Publication Date: 2018-08
• Subjects: MET exon 14 -- Multiple synchronous primary lung cancers -- Next generation sequencing -- Tumor evolution -- Subsolid pulmonary nodule; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2018.06.019
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Multiple synchronous lung cancers can be challenging to stage. We describe the first case of a patient with two lung cancers with distinct MET exon 14 mutations. The patient was staged as having two separate 1 A tumors and spared of adjuvant chemotherapy. Molecular analyses and radiographic criteria may offer more accurate staging and prognostication in these cases. Abstract: When a patient is found to have multiple lung tumors, distinguishing whether they represent metastatic nodules or separate primary cancers is crucial for staging and therapy. We report the case of a 79-year-old patient with two surgically resected synchronous left upper lobe adenocarcinomas initially pathologically staged as T3 (IIB), indicating adjuvant chemotherapy should be recommended. However, the tumors appeared radiographically distinct, so next-generation sequencing was performed on each nodule. Each tumor harbored a different mesenchymal-to-epithelial transition ( MET ) exon 14 skipping mutation, an emerging targetable mutation, suggestive of distinct clonality. While the in frame protein deletion was the same in each tumor, the nucleotide base substitutions were different. Thus, the patient was down-staged to having two separate IA tumors, spared of adjuvant chemotherapy, and routine surveillance was recommended. This case highlights the utility of using molecular analysis in diagnosing and treating multifocal lung tumors, and the process of convergent molecular evolution toward a common oncogenic driver mutation. This is the first case of multiple synchronous lung tumors each harboring a distinct MET exon 14 splice site mutation.