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Endocrine Pathology

, Volume 30, Issue 3, pp 237–245 | Cite as

Neuroendocrine Neoplasms Associated with Germline Pathogenic Variants in the Homologous Recombination Pathway

  • Marta Szybowska
  • Ozgur Mete
  • Evan Weber
  • Josh Silver
  • Raymond H. KimEmail author
Article
  • 180 Downloads

Abstract

Neuroendocrine neoplasms (NENs) have been primarily associated with germline pathogenic variants in genes involved in chromatin remodeling (MEN1), cell cycle control (CDKN1B), PI3K/mTOR signaling (TSC1/2, PTEN) as well as pseudohypoxia (VHL, SDHx). Recent work has implicated various genes involved in DNA repair pathways in the pathophysiology of a subset of pancreatic neuroendocrine neoplasms, including BRCA2, via the homologous recombination pathway (HRD). To date, germline variants in other HRD pathway genes have not been described to contribute to NEN. PALB2, RAD51C, and BARD1 are additional tumor suppressor genes which also mediate repair of double stranded DNA breaks through the HRD pathway and are implicated in hereditary breast (PALB2; BARD1) and ovarian (RAD51C) cancer. Here we report three cases of NEN associated with germline pathogenic variants in PALB2 (pancreatic NEN), RAD51C (thymic NEN), and BARD1 (pancreaticoduodenal NEN) respectively, further linking the DNA repair pathway to NENs.

Notes

Acknowledgements

We would like to thank our patients for consenting to the writing of this report and also to Dr. William Foulkes for reviewing this manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 1.Fred A. Litwin Family Center in Genetic MedicineUniversity Health NetworkTorontoCanada
  2. 2.Department of Laboratory Medicine and PathobiologyUniversity Health Network, University of TorontoTorontoCanada
  3. 3.Medical GeneticsMcGill University Health CentreMontrealCanada
  4. 4.Department of Molecular GeneticsUniversity of TorontoTorontoCanada
  5. 5.Division of Medical Oncology, Department of MedicineUniversity of TorontoTorontoCanada
  6. 6.Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Fred. A. Litwin Centre in Genetic MedicineUniversity Health Network, University of TorontoTorontoCanada

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