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

• DOI: 10.1371/journal.pgen.1005467
• Publication Date: 2015-08-21T20:09:06Z
• Authors: Jun Ho Ji; Young Lyun Oh; Mineui Hong; Jae Won Yun; Hyun-Woo Lee; DeokGeun Kim; Yongick Ji; Duk-Hwan Kim; Woong-Yang Park; Hyun-Tae Shin; Kyoung-Mee Kim; Myung-Ju Ahn; Keunchil Park; Jong-Mu Sun
• Keywords: Medullary Thyroid Cancer; Sanger sequencing

The genetic landscape of medullary thyroid cancer (MTC) is not yet fully understood, although some oncogenic mutations have been identified. To explore profiles MTCs, formalin-fixed, paraffin-embedded tumor tissues from MTC patients were assayed on the Ion AmpliSeq Cancer Panel v2. Eighty-four sporadic samples and 36 paired normal successfully sequenced. We discovered 101 hotspot in 18 genes 84 tissue samples. most common mutation was ret proto-oncogene, which occurred 47 cases followed by encoding Harvey rat sarcoma viral oncogene homolog (N = 14), serine/threonine kinase 11 11), v-kit Hardy-Zuckerman 4 feline 6), mutL 1 4), Kiesten 3) MET proto-oncogene 3). also evaluated anaplastic lymphoma (ALK) rearrangement immunohistochemistry break-apart fluorescence situ hybridization (FISH). Two 98 screened positive for ALK FISH. identify genomic breakpoint 5' fusion partner ALK, customized targeted panel sequencing performed using DNA two patients. Glutamine:fructose-6-phosphate transaminase (GFPT1)-ALK echinoderm microtubule-associated protein-like (EML4)-ALK fusions Additional PCR analysis, Sanger sequencing, confirmed GFPT1-ALK fusion, indicating that a result intra-chromosomal translocation or deletion. Notably, metastatic case harboring EML4-ALK showed dramatic response to an inhibitor, crizotinib. In conclusion, we found several are first MTC. Our results suggest may be potential driver valid target inhibitors. Furthermore, candidate molecular therapy.