Clonal Origin Evaluated by Trunk and Branching Drivers and Prevalence of Mutations in Multiple Lung Tumor Nodules
| Autor: | Rena Xian, Federico De Marchi, Peter B. Illei, Deborah A. Belchis, Jialing Haung, Christopher D. Gocke, Erika F. Rodriguez, James R. Eshleman, Li Hui Tseng, Ming Tseh Lin |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Neuroblastoma RAS viral oncogene homolog Pathology medicine.medical_specialty Lung Neoplasms Concordance Adenocarcinoma Biology medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Prevalence Genetics medicine Humans Pharmacology Lung High-Throughput Nucleotide Sequencing General Medicine Molecular medicine Trunk Human genetics 030104 developmental biology medicine.anatomical_structure Genes 030220 oncology & carcinogenesis Mutation Molecular Medicine Lung tumor KRAS Tumor Suppressor Protein p53 |
| Zdroj: | Molecular Diagnosis & Therapy. 24:461-472 |
| ISSN: | 1179-2000 1177-1062 |
| DOI: | 10.1007/s40291-020-00471-w |
| Popis: | Differentiation between intrapulmonary metastasis (IPM) and multiple primary lung cancers (MPLC) in patients with synchronous or metachronous lung tumor nodules is critical but challenging. We proposed an algorithm to evaluate clonal origin based on trunk (initiating) versus branching drivers and the prevalence of mutations in lung adenocarcinomas. Driver mutations were examined using next-generation sequencing in five trunk driver genes (BRAF, EGFR, ERBB2, KRAS, and NRAS) and three branching driver genes (ATK1, PIK3CA, and TP53). Mutational profiling supported same clonality and likely same clonality, respectively, in 39 and 14 of 66 pairs of specimens with known identical clonal origin. Discordance of TP53 mutations (branching drivers) was observed in three pairs. Subsequent analyses of 30 pairs of synchronous or metachronous lung tumor nodules revealed different clonality and likely different clonality in 17 and 2 pairs, respectively, including three pairs with similar histomorphology; same clonality and likely same clonality in three and five pairs, respectively, including two pairs with different histomorphology; and inconclusive or noninformative results in three pairs. While discordance of trunk drivers indicated MPLC in patients with synchronous or metachronous lung tumor nodules, discordance of branching drivers did not exclude IPM. Concordance of uncommon drivers supported IPM, whereas concordance of common drivers did not exclude MPLC. Additional recommendations from official organizations are needed to guide applications of molecular markers in defining clonality of multiple lung tumor nodules. |
| Databáze: | OpenAIRE |
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