Related Experiment Video

Updated: Jun 25, 2025

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
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Published on: April 4, 2018

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Germline NPAT inactivating variants as cause of hereditary colorectal cancer

Mariona Terradas1,2, Stephanie A Schubert3, Julen Viana-Errasti1

  • 1Hereditary Cancer Programme, Catalan Institute of Oncology; Oncobell Programme, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.

European Journal of Human Genetics : EJHG
|May 22, 2024
PubMed

Insights

Genetic variants in the NPAT gene may predispose individuals to nonpolyposis colorectal cancer. Inactivating NPAT variants were found in families with colorectal cancer, suggesting a link to disease predisposition.

Area of Science:

  • Genetics and Oncology
  • Molecular Biology

Background:

  • Colorectal cancer (CRC) predisposition is linked to various genetic factors.
  • Identifying novel genes associated with familial or early-onset CRC is crucial for understanding disease mechanisms.

Purpose of the Study:

  • To identify new genes predisposing to nonpolyposis colorectal cancer.
  • To investigate the role of NPAT gene variants in colorectal cancer susceptibility.

Main Methods:

  • Exome sequencing initiatives to identify causative variants.
  • Comparative analysis of NPAT variants in familial CRC patients versus control populations (gnomAD).
  • Assessment of chromosomal instability and aneuploidy levels in colorectal tumors with NPAT variants.

Main Results:

  • Heterozygous loss-of-function variants in the NPAT gene were identified in two families with multiple colorectal cancer cases.
  • Enrichment of NPAT loss-of-function and deleterious variants was observed in familial/early-onset CRC patients.
  • Colorectal cancers with somatic NPAT variants showed higher aneuploidy levels, especially in the absence of DNA repair defects.

Conclusions:

  • Constitutional inactivating NPAT variants are associated with predisposition to mismatch repair-proficient nonpolyposis colorectal cancer.
  • NPAT plays a role in maintaining genomic stability, and its dysfunction contributes to colorectal tumorigenesis.

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