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Lung Cancer. 2018 Aug;122:187-191. doi: 10.1016/j.lungcan.2018.06.019. Epub 2018 Jun 15.

Synchronous primary lung adenocarcinomas harboring distinct MET Exon 14 splice site mutations.

Author information

1
Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA, United States.
2
Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States.
3
Department of Radiology, Stanford University School of Medicine, Stanford, CA, United States.
4
Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, United States.
5
Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA, United States. Electronic address: jwneal@stanford.edu.

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.

KEYWORDS:

MET exon 14; Multiple synchronous primary lung cancers; Next generation sequencing; Subsolid pulmonary nodule; Tumor evolution

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