Genetic Cause Found for Rare Aggressive Ovarian Cancer
By LabMedica International staff writers Posted on 09 Apr 2014 |
Image: Histopathology of small cell carcinoma of the ovary, hypercalcemic type; the tumor cells are arranged in small nests (Photo courtesy of Dr. Dharam Ramnani).
The genetic cause of a rare type of ovarian cancer known as small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), that most often strikes girls and young women has been revealed.
This type of cancer, SCCHOT, usually is not diagnosed until it is in its advanced stages and it does not respond to standard chemotherapy, and 65% of patients die within two years. It can affect girls as young as 14 months, and women as old as 58 years, with a mean age of only 24 years old.
An international team led by the Translational Genomics Research Institute (TGen; Phoenix, AZ, USA) analyzed the genetic etiology of SCCOHT by performing next-generation sequencing on a series of tumors and germline samples from 12 SCCOHT cases. This included nine tumors with four matched germline samples and three additional germline samples, and on the SCCOHT cell line BIN-67. DNA from tumor and blood specimens was analyzed using whole-genome sequencing and whole-exome sequencing.
Genomic DNA from each sample was fragmented to a target size of 300 to 350 base pairs (bp). After ligation, samples were run on a gel to separate products and the products were quantified using the High-Sensitivity DNA chip on an Agilent 2100 Bioanalyzer (Santa Clara, CA, USA). A tissue microarray (TMA) representing nine SCCOHT cases was fabricated at TGen for the study. Protein blot analysis was performed on whole cell extracts.
The scientists identified frequent germline and somatic gene SWItch/Sucrose NonFermentable (SWI/SNF) Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily A, Member 4 (SMARCA4) mutations and SMARCA4 protein loss in SCCOHT. The loss of SMARCA4 protein expression is extremely specific to SCCOHT and can facilitate the differential diagnosis of SCCOHT.
Jeffrey Trent, PhD, President and Research Director of TGen, and the study's senior author, said, “This is a thoroughly remarkable study. Many genetic anomalies can be like a one-lane road to cancer; difficult to negotiate. But these findings indicate a genetic superhighway that leads right to this highly aggressive disease. The correlation between mutations in SMARCA4 and the development of SCCOHT is simply unmistakable.” The study was published on March 23, 2014, in the journal Nature Genetics.
Related Links:
Translational Genomics Research Institute
Agilent
This type of cancer, SCCHOT, usually is not diagnosed until it is in its advanced stages and it does not respond to standard chemotherapy, and 65% of patients die within two years. It can affect girls as young as 14 months, and women as old as 58 years, with a mean age of only 24 years old.
An international team led by the Translational Genomics Research Institute (TGen; Phoenix, AZ, USA) analyzed the genetic etiology of SCCOHT by performing next-generation sequencing on a series of tumors and germline samples from 12 SCCOHT cases. This included nine tumors with four matched germline samples and three additional germline samples, and on the SCCOHT cell line BIN-67. DNA from tumor and blood specimens was analyzed using whole-genome sequencing and whole-exome sequencing.
Genomic DNA from each sample was fragmented to a target size of 300 to 350 base pairs (bp). After ligation, samples were run on a gel to separate products and the products were quantified using the High-Sensitivity DNA chip on an Agilent 2100 Bioanalyzer (Santa Clara, CA, USA). A tissue microarray (TMA) representing nine SCCOHT cases was fabricated at TGen for the study. Protein blot analysis was performed on whole cell extracts.
The scientists identified frequent germline and somatic gene SWItch/Sucrose NonFermentable (SWI/SNF) Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily A, Member 4 (SMARCA4) mutations and SMARCA4 protein loss in SCCOHT. The loss of SMARCA4 protein expression is extremely specific to SCCOHT and can facilitate the differential diagnosis of SCCOHT.
Jeffrey Trent, PhD, President and Research Director of TGen, and the study's senior author, said, “This is a thoroughly remarkable study. Many genetic anomalies can be like a one-lane road to cancer; difficult to negotiate. But these findings indicate a genetic superhighway that leads right to this highly aggressive disease. The correlation between mutations in SMARCA4 and the development of SCCOHT is simply unmistakable.” The study was published on March 23, 2014, in the journal Nature Genetics.
Related Links:
Translational Genomics Research Institute
Agilent
Latest Molecular Diagnostics News
- New Respiratory Syndromic Testing Panel Provides Fast and Accurate Results
- New Synthetic Biomarker Technology Differentiates Between Prior Zika and Dengue Infections
- Novel Biomarkers to Improve Diagnosis of Renal Cell Carcinoma Subtypes
- RNA-Powered Molecular Test to Help Combat Early-Age Onset Colorectal Cancer
- Advanced Blood Test to Spot Alzheimer's Before Progression to Dementia
- Multi-Omic Noninvasive Urine-Based DNA Test to Improve Bladder Cancer Detection
- First of Its Kind NGS Assay for Precise Detection of BCR::ABL1 Fusion Gene to Enable Personalized Leukemia Treatment
- 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