A Specific Mutation Links Some Forms of Inherited Melanoma
|
By LabMedica International staff writers Posted on 09 Apr 2014 |
|
![Image: Melanoma on a patient\'s skin (Photo courtesy of the [US] National Cancer Institute).](https://globetechcdn.com/mobile_labmedica/images/stories/articles/article_images/2014-04-09/GMS-097.jpg "Image: Melanoma on a patient\'s skin (Photo courtesy of the [US] National Cancer Institute).")
Image: Melanoma on a patient\'s skin (Photo courtesy of the [US] National Cancer Institute).
A mutation that inactivates the POT1 (protection of telomeres 1) gene has been linked to the development of an inherited form of melanoma.
The POT1 gene encodes for synthesis of "protection of telomeres protein 1" protein, a nuclear protein involved in telomere maintenance. This protein functions as a member of a multiprotein complex that binds to the TTAGGG repeats of telomeres, regulating telomere length and protecting chromosome ends from illegitimate recombination, catastrophic chromosome instability, and abnormal chromosome segregation.
Investigators at the Wellcome Trust Sanger Institute (Hinxton, United Kingdom) and the University of Leeds (United Kingdom) searched for unrecognized promelanoma genes by sequencing the DNA from184 melanoma patients from 105 families recruited in the United Kingdom, The Netherlands, and Australia that were negative for variants in genes known to be linked to predisposition for developing melanoma.
They identified families where melanoma co-segregated with loss-of-function variants in the POT1gene, with a proportion of family members presenting with an early age of onset and multiple primary tumors. They showed that these variants either affected POT1 mRNA splicing or altered key residues in the highly conserved oligonucleotide/oligosaccharide-binding domains of POT1, disrupting protein-telomere binding and leading to increased telomere length. These findings suggest that POT1 variants predispose to melanoma formation via a direct effect on telomeres.
"Genomics is on the verge of transforming the healthcare system – this study highlights the potential clinical benefits that can be gained through genomic studies and offers potential strategies to improve patient care and disease management," said senior author Dr. David Adams, leader of the experimental cancer genetics program at the Wellcome Trust Sanger Institute. "With this discovery we should be able to determine who in a family is at risk, and in turn, who should be regularly screened for early detection."
The article linking POT1 mutations to melanoma was published in the March 30, 2014, online edition of the journal Nature Genetics.
Related Links:
Wellcome Trust Sanger Institute
University of Leeds
The POT1 gene encodes for synthesis of "protection of telomeres protein 1" protein, a nuclear protein involved in telomere maintenance. This protein functions as a member of a multiprotein complex that binds to the TTAGGG repeats of telomeres, regulating telomere length and protecting chromosome ends from illegitimate recombination, catastrophic chromosome instability, and abnormal chromosome segregation.
Investigators at the Wellcome Trust Sanger Institute (Hinxton, United Kingdom) and the University of Leeds (United Kingdom) searched for unrecognized promelanoma genes by sequencing the DNA from184 melanoma patients from 105 families recruited in the United Kingdom, The Netherlands, and Australia that were negative for variants in genes known to be linked to predisposition for developing melanoma.
They identified families where melanoma co-segregated with loss-of-function variants in the POT1gene, with a proportion of family members presenting with an early age of onset and multiple primary tumors. They showed that these variants either affected POT1 mRNA splicing or altered key residues in the highly conserved oligonucleotide/oligosaccharide-binding domains of POT1, disrupting protein-telomere binding and leading to increased telomere length. These findings suggest that POT1 variants predispose to melanoma formation via a direct effect on telomeres.
"Genomics is on the verge of transforming the healthcare system – this study highlights the potential clinical benefits that can be gained through genomic studies and offers potential strategies to improve patient care and disease management," said senior author Dr. David Adams, leader of the experimental cancer genetics program at the Wellcome Trust Sanger Institute. "With this discovery we should be able to determine who in a family is at risk, and in turn, who should be regularly screened for early detection."
The article linking POT1 mutations to melanoma was published in the March 30, 2014, online edition of the journal Nature Genetics.
Related Links:
Wellcome Trust Sanger Institute
University of Leeds
Platinum Member
Automated Coagulation Analyzer
Hemolumi H6
CMV CLIA Diagnostic
CLIA CMV IgA Screen Group
Gold Member
Neonatal Heel Incision Device
Tenderfoot
Latest Pathology News
- AI Tissue Analysis May Help Identify Missed Precancerous Colon Polyps
- AI Pre-Screening Helps Identify Lung Cancer Cases for Additional Biomarker Testing
- AI Pathology Platform Targets Workflow Delays and Molecular Test Failures
- Updated Digital Pathology Platform Expands AI Integration for Cancer Diagnosis
- Molecular Testing Refines Barrett’s Esophagus Progression Risk Beyond Biopsy Findings
- AI Histopathology Tool Distinguishes Ewing Sarcoma for Diagnosis
- Rapid Mass Spectrometry Test May Aid Glioma Margin Decisions
- Genomic Classifier Predicts Benefit From Adding Hormone Therapy to Salvage Prostate Radiation
- Multimodal AI Supports Prostate Cancer Risk Assessment Across Diverse Cohorts
- New AI Model Maps Where Glioblastoma Could Return After Surgery
- Simple Test Could Reduce the Need for Invasive Uterine Cancer Checks
- Tumor Blood Vessel Features May Help Predict Colorectal Cancer Survival
- Multimodal AI Improves Breast Cancer Recurrence Risk Prediction Beyond Standard Genomic Testing
- Machine Learning Cytology Tool Improves Cancer Cell Identification
- CAP Updates Cancer Protocols to Refine Breast Cancer Biomarker Reporting and GIST Molecular Testing
- Tumor Budding Grading May Predict Chemotherapy Benefit in Resected Lung Squamous Cancer
Channels
Clinical Chemistry
view channel
Daily Blood Biomarker Testing May Help Guide Earlier Antibiotic Stopping in Sepsis
Sepsis is a life-threatening condition caused by the body’s overwhelming response to infection and accounts for thousands of deaths each year. In intensive care, concern about stopping treatment too early... Read more
Blood Proteins Reveal Signals Linked to Prostate Cancer Risk Years Before Diagnosis
Prostate cancer is the most commonly diagnosed cancer in men worldwide. While many tumors grow slowly, aggressive forms can be life-threatening, underscoring the need for earlier risk identification.... Read more
Two-Step Blood Testing Approach Reduces Uncertainty in Amyloid Assessment
Blood-based biomarkers offer a more accessible, less expensive way to detect Alzheimer’s-related brain changes than traditional methods such as amyloid-beta positron emission tomography (Aβ-PET).... Read more
Multimodal Platform to Combine Blood and Imaging Biomarkers for Lung Nodule Assessment
Lung nodules are commonly detected during chest imaging and require careful risk assessment to determine whether follow-up imaging, additional testing, or biopsy is needed. With millions of patients evaluated... Read moreHematology
view channel
New Myelofibrosis Guidelines Recommend Expanded Genetic Testing at Diagnosis
Myelofibrosis is a rare, life-threatening blood cancer affecting up to six per 100,000 people. The disease causes scarring in the bone marrow, limiting the production of healthy blood cells and potentially... Read more
Handheld Point-of-Care Test Aims to Enable Rapid Coagulation Assessment in Trauma
Severe blood loss and inadequate tissue oxygenation are leading causes of preventable death after traumatic injury. Blood products are essential in trauma care, but cold-chain storage, short shelf life,... Read more
Immunology
view channel
Antibody Profiling Predicts Inflammatory Bowel Disease Years Before Diagnosis
Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, involves abnormal immune responses that cause persistent inflammation and damage in the digestive system.... Read more
Immune Profiling Initiative Aims to Improve Bone Marrow Analysis in Leukemia
Acute myeloid leukemia (AML) is an aggressive blood cancer in which assessing disease burden after therapy can help guide clinical evaluation. Patients with measurable residual disease (MRD) after treatment... Read more
Immune Profiling Identifies Early Maternal Autoantibodies Linked to Preterm Birth Risk
A typical pregnancy lasts about 40 weeks, but labor begins prematurely in roughly one in 10 pregnancies. Preterm birth is the leading cause of newborn death worldwide, yet its underlying causes and which... Read more
Longitudinal Blood Testing Reveals Changes in Allergen Sensitization During Childhood
Food allergy is a major childhood health concern, and distinguishing persistent risk from transient sensitization can guide clinical decisions. Specific IgE antibodies may be detectable even when a child... Read moreMicrobiology
view channel
Molecular Panel Gains WHO Emergency Use Listing to Support Ebola Outbreak Response
The ongoing Ebola Bundibugyo outbreak in the Democratic Republic of the Congo and neighboring countries has become one of the largest outbreaks of this Ebola virus species recorded to date.... Read more
Rapid Host-Response Test Aims to Predict Corticosteroid Benefit in Sepsis
Sepsis and severe infections are difficult to treat because patients with similar clinical presentations may have very different underlying immune responses. Corticosteroids are commonly used in severe... Read more
Pathology
view channel
AI Tissue Analysis May Help Identify Missed Precancerous Colon Polyps
Colorectal cancer is diagnosed in an estimated 1.9 million people worldwide each year, often without symptoms in its early stages. Timely detection of precancerous lesions is therefore important, yet some... Read more
AI Pre-Screening Helps Identify Lung Cancer Cases for Additional Biomarker Testing
Tempus AI (Chicago, IL, USA) will present findings from a study evaluating an artificial intelligence (AI)-enabled pre-screening panel for advanced non-small cell lung cancer (NSCLC) at the ESMO Congress... Read more
AI Pathology Platform Targets Workflow Delays and Molecular Test Failures
Pathology laboratories often rely on visual review of tissue slides to assess quality, identify tumors, count mitoses, and estimate tumor content. These tasks can be time-consuming and vary between readers,... Read more
Molecular Testing Refines Barrett’s Esophagus Progression Risk Beyond Biopsy Findings
Barrett’s esophagus is a precancerous condition associated with increased risk of esophageal adenocarcinoma. Routine endoscopic biopsy findings guide surveillance and therapy, but histopathology may not... Read moreTechnology
view channel
New AI-Powered System Aims to Streamline Laboratory and Manufacturing Workflows
Scientific laboratories supporting drug development, biotechnology, and materials research increasingly rely on coordinated digital workflows to move data, samples, and activities across teams.... Read more
Laser-Based Swab Analysis Shows Promise for Detecting Disease-Linked Odor Patterns
Disease-related changes in volatile organic compounds can alter body odor, producing measurable patterns in exhaled breath and bodily fluids. Current analytical methods can be complex, time-consuming,... Read more
Industry
view channel
Collaboration to Expand Cervical Cancer Screening Access With At-Home HPV Collection
Cervical cancer is largely preventable with regular screening and early detection of human papillomavirus (HPV), the leading cause of the disease. Screening gaps persist, in part because traditional sample... Read more
Alzheimer’s Progression Blood Test Gains U.S. Patent Ahead of Planned Launch
Alzheimer’s disease is the most common cause of dementia, accounting for an estimated 60–70% of cases worldwide. Its progressive effects on memory, thinking, behavior, and daily functioning underscore... Read more
