Unraveling the Causes of Small Intestinal NETs

The first step in curing a disease is understanding it. Unfortunately, there is a lot we still don’t know about small-intestinal  NETs (SI-NETs). That’s why NETRF invested in an international team to look for a cause.

Researchers will work to answer these questions:

  • Is a genomic mutation for SI-NETs passed down from parent to child?
  • Does something sporadically go wrong during a normal cellular process, like a production error on an assembly line, leading a gene to be copied incorrectly —maybe part of the code gets dropped, added, or transposed?
  • Does a genomic mutation result from environmental exposure, similar to the way lung cancer can be caused by smoking and skin cancer can be caused by sun exposure?
  • Is an infectious agent responsible for damaging a healthy gene in a way that could give rise to NETs — the way HPV contributes to head, neck, and cervical cancers?

Principal Investigators

  • Matthew Meyerson, MD, PhD, Director of Cancer Genomics at Dana-Farber Cancer Institute, Professor of Pathology at Harvard Medical School, Director of Cancer Genomics at the Broad Institute.
  • Eric Nakakura, MD, PhD, Gastrointestinal Oncology Surgeon, Professor of Surgery, at University of California, San Francisco.
  • Chrissie Thirlwell, MD, PhD, FRCP, Senior Lecturer and Consultant, Medical Oncologist, University College London Cancer Institute and Royal Free Hospital.

Thus far, the team has sequenced over 80 different SI-NETs specimens to study how all the genes in each of these tumors are expressed, and, are now analyzing gene expression patterns common to SI-NETs from different individuals but different from other types of cancers.

This will answer a fundamental question: Do SI-NETs form a unique class of tumors, with a unique molecular profile?

Specific Aims of the Study

This NETRF Accelerator Grant, “Finding the causes of small intestinal neuroendocrine tumors”  got underway in 2017 and will continue through 2021. This is the team's plan to look for the genomic causes for small intestinal NETs.

  • The research team will analyze tumor specimens collected and preserved by Eric Nakakura, MD, PhD, surgical oncologist at University of California, San Francisco, using next-generation genomic sequencing performed at the Broad Institute lab of Matthew Meyerson, MD, PhD. Researchers will analyze the enormous amount of data produced from the genomic sequencing to identify patterns:
    • What inherited and acquired genomic mutations appear in the specimens?
    • Are they known to contribute to cancer?
    • How many specimens share the same errors?
  • The SI-NET tumor specimens will then be sequenced differently to analyze possible epigenetic causes. Chrissie Thirlwell’s lab at University College London Cancer Institute will look for evidence of gene expression errors. Genes use a complex communication system to give cells instructions.
    • Maybe a gene isn’t altered, but something goes wrong in how the gene is expressed.
    • A person’s environment, lifestyle, age, and more can influence gene expression.

To support essential NET research like this, give to NETRF.