Identification of Driving Fusion Genes and Genomic Landscape of Medullary Thyroid Cancer

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Little is known about the molecular biology of medullary thyroid cancer (MTC), which is a rare disease. Genomics are increasingly being used to improve our knowledge about disease biology and to identify therapeutic targets in many cancers. Here, we report the largest genomic results of MTC to date. MTC tissue frequently included several mutations. For the first time, anaplastic lymphoma kinase (ALK) rearrangements were detected in MTC: one case with a glutamine:fructose-6-phosphate transaminase 1 (GFPT1)-ALK fusion, and another case with an echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion. The fusion mechanism of the novel GFPT1-ALK fusion was successfully investigated using molecular biology techniques. In addition, an inhibitor of ALK (crizotinib) dramatically decreased the number of metastatic MTC lesions harboring the EML4-ALK fusion, thus verifying the fusion as a promising target in MTC. Our findings suggest that using rapidly improving sequencing techniques and accumulated genomic data to comprehensively perform genetic analyses on rare tumors, such as MTC, will help to improve the poor prognosis of orphan diseases.

Vyšlo v časopise: Identification of Driving Fusion Genes and Genomic Landscape of Medullary Thyroid Cancer. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005467
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005467

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