Recently, the PARP4 gene has been identified as a possible susceptibility gene of primary thyroid and breast cancers. We analyzed PARP4 in 53 patients with multiple primary cancers including a thyroid cancer (TC), in 74 patients with TC alone, and in 88 healthy donors. Two PARP4 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 PARP4 pseudogene (PARP4P2) in one patient with four primary tumors, and with a familial cancer history. PARP4 mRNA was absent in all primary tumors and matched normal tissues, whereas the pseudogene variant transcript was always expressed. Consistently, immunostaining for PARP4 protein was negative at nuclear level in all tissues, thus suggesting that PARP4P2 pseudogene variant could alter its regulatory role on PARP4, inducing the down-regulation of PARP4 expression at both tumor and normal tissues level. In conclusion, germline intronic PARP4 variants could be a risk factor for the development of TC, and PARP4P2 pseudogene variations associated with PARP4 down-regulation may confer susceptibility to develop multiple metachronous cancers.

Genetic variants of PARP4 gene and PARP4P2 pseudogene in patients with multiple primary tumors including thyroid cancer / V. Cirello, C. Colombo, G. Pogliaghi, M. Proverbio, S. Rossi, E. Mussani, D. Tosi, G. Bulfamante, E. Bonoldi, G. Gherardi, L. Persani, L. Fugazzola. - In: MUTATION RESEARCH. FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS. - ISSN 1386-1964. - 816-818,(2019 Nov). [10.1016/j.mrfmmm.2019.111672]

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

V. Cirello
Primo
;
C. Colombo;G. Pogliaghi;M. Proverbio;D. Tosi;G. Bulfamante;L. Persani
Penultimo
;
L. Fugazzola
Ultimo
2019-11

Abstract

Recently, the PARP4 gene has been identified as a possible susceptibility gene of primary thyroid and breast cancers. We analyzed PARP4 in 53 patients with multiple primary cancers including a thyroid cancer (TC), in 74 patients with TC alone, and in 88 healthy donors. Two PARP4 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 PARP4 pseudogene (PARP4P2) in one patient with four primary tumors, and with a familial cancer history. PARP4 mRNA was absent in all primary tumors and matched normal tissues, whereas the pseudogene variant transcript was always expressed. Consistently, immunostaining for PARP4 protein was negative at nuclear level in all tissues, thus suggesting that PARP4P2 pseudogene variant could alter its regulatory role on PARP4, inducing the down-regulation of PARP4 expression at both tumor and normal tissues level. In conclusion, germline intronic PARP4 variants could be a risk factor for the development of TC, and PARP4P2 pseudogene variations associated with PARP4 down-regulation may confer susceptibility to develop multiple metachronous cancers.
Settore MED/13 - Endocrinologia
giu-2019
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/655454
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