Identification of Three Novel Fusion Oncogenes, SQSTM1/NTRK3, AFAP1L2/RET, and PPFIBP2/RET in Thyroid Cancers of Young Patients in Fukushima.

Identification of Three Novel Fusion Oncogenes, SQSTM1/NTRK3, AFAP1L2/RET, and PPFIBP2/RET in Thyroid Cancers of Young Patients in Fukushima.

Thyroid. 2017 Mar 29;:

Authors: Iyama K, Matsuse M, Mitsutake N, Rogounovitch T, Saenko VA, Suzuki K, Ashizawa M, Ookouchi C, Suzuki S, Mizunuma H, Fukushima T, Suzuki S, Yamashita S

Abstract
BACKGROUND: The BRAFV600E mutation is the most frequent genetic abnormality in adult papillary thyroid carcinomas (PTCs). On the other hand, various chromosomal rearrangements are more prevalent in childhood and adolescent PTCs. The aim of the present study was to identify novel rearrangements in PTCs from young patients.
METHODS: Among 63 postoperative specimens of childhood and adolescent PTCs, which had been discovered by the thyroid ultrasound screening program in Fukushima, 9 samples without prevalent known oncogenes, BRAFV600E, RAS, RET/PTC1, RET/PTC3, and ETV6/NTRK3 were analyzed in the current study by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) to screen for novel fusion genes by comparing transcript expression between extracellular and kinase domains of ALK, NTRK1, NTRK3, and RET.
RESULTS: Of the above nine samples, five samples were suspected to harbor a fusion, and using subsequent 5' rapid amplification of cDNA end (RACE), we identified two already reported fusion oncogenes, STRN/ALK and TPR/NTRK1, and three novel fusions, SQSTM1/NTRK3, AFAP1L2/RET, and PPFIBP2/RET. We performed functional analyses of these three chimeric genes and confirmed their transforming abilities through the activation of mitogen-activated protein kinase (MAPK).
CONCLUSIONS: we have identified three novel fusion oncogenes in young PTC patients in Fukushima, suggesting that rare fusions may be present among the cases negative for known oncogenes in this age group and that such rearrangements can play a significant role in thyroid carcinogenesis.

PMID: 28351223 [PubMed - as supplied by publisher]

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