Genetic variants of PARP4 gene and PARP4P2 pseudogene in patients with multiple primary tumors including thyroid cancer.

Recently, the gene has been identified as a possible susceptibility gene of primary thyroid and breast cancers. We analyzed Pduanyu374 in 53 patients with multiple primary cancers including a thyroid cancer (TC), in 74 patients with TC alone, and in 88 healthy donors. Two Pduanyu374 intronic variants within the IVS29 (c.3543 + 44T > C) and the IVS22 (c.2758 + 9G > A) were found only in the two patient groups. Moreover, we found a rare variant (r.522C > A) within a Pduanyu374 pseudogene in one patient with four primary tumors, and with a familial cancer history. Pduanyu374 mRNA was absent in all primary tumors and matched normal tissues, whereas the pseudogene variant transcript was always expressed. Consistently, immunostaining for Pduanyu374 protein was negative at nuclear level in all tissues, thus suggesting that pseudogene variant could alter its regulatory role on inducing the down-regulation of Pduanyu374 expression at both tumor and normal tissues level. In conclusion, germline intronic Pduanyu374 variants could be a risk factor for the development of TC, and Pduanyu374P2 pseudogene variations associated with Pduanyu374 down-regulation may confer susceptibility to develop multiple metachronous cancers.

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