Mutations Linked to Familial Pancreatic Cancer Identified
By LabMedica International staff writers Posted on 28 Aug 2019 |
Image: A histopathology of pancreatic cancer; Scientists studying a highly cancer-prone family have identified a rare, inherited gene mutation that dramatically raises the lifetime risk of pancreatic and other cancers (Photo courtesy of the Dana-Farber Cancer Institute).
Pancreatic ductal adenocarcinoma is an aggressive cancer with limited treatment options. Approximately 10% of cases exhibit familial predisposition, but causative genes are not known in most families.
Pancreatic cancer is one of the deadliest cancers with limited treatment options. It typically comes with an especially poor prognosis due to its lack of symptoms until advanced stages and its ability to resist many anticancer therapies. Identifying genes involved in its development may lead to earlier diagnoses and improved treatments.
A team of scientists working with the Massachusetts General Hospital (Boston, MA, USA) performed whole-genome sequence analysis in a family with multiple cases of pancreatic ductal adenocarcinoma and identify a germline truncating mutation in the member of the RAS oncogene family-like 3 (RABL3) gene. Transcriptomic and mass spectrometry approaches implicate RABL3 in RAS pathway regulation and identify an interaction with RAP1GDS1 (SmgGDS), a chaperone regulating prenylation of RAS GTPases.
The truncated mutant RABL3 protein accelerates KRAS prenylation and requires RAS proteins to promote cell proliferation. Finally, evidence in patient cohorts with developmental disorders implicates germline RABL3 mutations in RASopathy syndromes. The studies identified RABL3 mutations as a target for genetic testing in cancer families and uncover a mechanism for dysregulated RAS activity in development and cancer.
Sahar Nissim, MD, PhD, a cancer geneticist and gastroenterologist and lead author of the study, said, “More broadly, this work highlights the power of studying and understanding rare family syndromes: from just one family, we may gain precious clues to why pancreatic cancer happens, how we may prevent it or catch it earlier, and how we may treat it more effectively.” The study was published on August 12, 2019, in the journal Nature Genetics.
Related Links:
Massachusetts General Hospital
Pancreatic cancer is one of the deadliest cancers with limited treatment options. It typically comes with an especially poor prognosis due to its lack of symptoms until advanced stages and its ability to resist many anticancer therapies. Identifying genes involved in its development may lead to earlier diagnoses and improved treatments.
A team of scientists working with the Massachusetts General Hospital (Boston, MA, USA) performed whole-genome sequence analysis in a family with multiple cases of pancreatic ductal adenocarcinoma and identify a germline truncating mutation in the member of the RAS oncogene family-like 3 (RABL3) gene. Transcriptomic and mass spectrometry approaches implicate RABL3 in RAS pathway regulation and identify an interaction with RAP1GDS1 (SmgGDS), a chaperone regulating prenylation of RAS GTPases.
The truncated mutant RABL3 protein accelerates KRAS prenylation and requires RAS proteins to promote cell proliferation. Finally, evidence in patient cohorts with developmental disorders implicates germline RABL3 mutations in RASopathy syndromes. The studies identified RABL3 mutations as a target for genetic testing in cancer families and uncover a mechanism for dysregulated RAS activity in development and cancer.
Sahar Nissim, MD, PhD, a cancer geneticist and gastroenterologist and lead author of the study, said, “More broadly, this work highlights the power of studying and understanding rare family syndromes: from just one family, we may gain precious clues to why pancreatic cancer happens, how we may prevent it or catch it earlier, and how we may treat it more effectively.” The study was published on August 12, 2019, in the journal Nature Genetics.
Related Links:
Massachusetts General Hospital
Latest Molecular Diagnostics News
- Urine Test to Revolutionize Lyme Disease Testing
- Simple Blood Test Could Enable First Quantitative Assessments for Future Cerebrovascular Disease
- New Genetic Testing Procedure Combined With Ultrasound Detects High Cardiovascular Risk
- Blood Samples Enhance B-Cell Lymphoma Diagnostics and Prognosis
- Blood Test Predicts Knee Osteoarthritis Eight Years Before Signs Appears On X-Rays
- Blood Test Accurately Predicts Lung Cancer Risk and Reduces Need for Scans
- Unique Autoantibody Signature to Help Diagnose Multiple Sclerosis Years before Symptom Onset
- Blood Test Could Detect HPV-Associated Cancers 10 Years before Clinical Diagnosis
- Low-Cost Point-Of-Care Diagnostic to Expand Access to STI Testing
- 18-Gene Urine Test for Prostate Cancer to Help Avoid Unnecessary Biopsies
- Urine-Based Test Detects Head and Neck Cancer
- Blood-Based Test Detects and Monitors Aggressive Small Cell Lung Cancer
- Blood-Based Machine Learning Assay Noninvasively Detects Ovarian Cancer
- Simple PCR Assay Accurately Differentiates Between Small Cell Lung Cancer Subtypes
- Revolutionary T-Cell Analysis Approach Enables Cancer Early Detection
- Single Genetic Test to Accelerate Diagnoses for Rare Developmental Disorders