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

Valentina Cirello, Carla Colombo, Gabriele Pogliaghi, Maria Carla Proverbio, Stefania Rossi, Elena Mussani, Delfina Tosi, Gaetano Bulfamante, Emanuela Bonoldi, Giorgio Gherardi, Luca Persani, Laura Fugazzola

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number111672
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Publication statusPublished - Nov 2019


  • DNA repair
  • Multiple primary tumors
  • PARP4
  • PARP4P2
  • Pseudogene
  • Thyroid cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis


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