Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact

Citations to this article

PALLD mutation in a European family conveys a stromal predisposition for familial pancreatic cancer
Lucia Liotta, … , Maximilian Reichert, Michael Quante
Lucia Liotta, … , Maximilian Reichert, Michael Quante
Published March 25, 2021
Citation Information: JCI Insight. 2021;6(8):e141532. https://doi.org/10.1172/jci.insight.141532.
View: Text | PDF
Clinical Medicine Gastroenterology Oncology

PALLD mutation in a European family conveys a stromal predisposition for familial pancreatic cancer

  • Text
  • PDF
Abstract

BACKGROUND Pancreatic cancer is one of the deadliest cancers, with low long-term survival rates. Despite recent advances in treatment, it is important to identify and screen high-risk individuals for cancer prevention. Familial pancreatic cancer (FPC) accounts for 4%–10% of pancreatic cancers. Several germline mutations are related to an increased risk and might offer screening and therapy options. In this study, we aimed to identity of a susceptibility gene in a family with FPC.METHODS Whole exome sequencing and PCR confirmation was performed on the surgical specimen and peripheral blood of an index patient and her sister in a family with high incidence of pancreatic cancer, to identify somatic and germline mutations associated with familial pancreatic cancer. Compartment-specific gene expression data and immunohistochemistry were also queried.RESULTS The identical germline mutation of the PALLD gene (NM_001166108.1:c.G154A:p.D52N) was detected in the index patient with pancreatic cancer and the tumor tissue of her sister. Whole genome sequencing showed similar somatic mutation patterns between the 2 sisters. Apart from the PALLD mutation, commonly mutated genes that characterize pancreatic ductal adenocarcinoma were found in both tumor samples. However, the 2 patients harbored different somatic KRAS mutations (G12D and G12V). Healthy siblings did not have the PALLD mutation, indicating a disease-specific impact. Compartment-specific gene expression data and IHC showed expression in cancer-associated fibroblasts (CAFs).CONCLUSION We identified a germline mutation of the palladin (PALLD) gene in 2 siblings in Europe, affected by familial pancreatic cancer, with a significant overexpression in CAFs, suggesting that stromal palladin could play a role in the development, maintenance, and/or progression of pancreatic cancer.FUNDING DFG SFB 1321

Authors

Lucia Liotta, Sebastian Lange, H. Carlo Maurer, Kenneth P. Olive, Rickmer Braren, Nicole Pfarr, Sebastian Burger, Alexander Muckenhuber, Moritz Jesinghaus, Katja Steiger, Wilko Weichert, Helmut Friess, Roland Schmid, Hana Algül, Philipp J. Jost, Juliane Ramser, Christine Fischer, Anne S. Quante, Maximilian Reichert, Michael Quante

×

Loading citation information...
Advertisement

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts