Molecular Makeup Uncovered in New Form of Cancer
By LabMedica International staff writers Posted on 25 Jun 2014 |
Image: The 3730xl DNA Analyzer (Photo courtesy of Applied Biosystems).
The molecular signature and genetic structure has been revealed of a new form of cancer that begins in the nose and is called biphenotypic sinonasal sarcoma (SNS).
The cancer, that appears to be most common in women, starts in the nose and can spread to the rest of the face, meaning the patient will need disfiguring surgery in order to survive, but by uncovering the molecular makeup of the tumor it was found that many existing cancer drugs that could be used to treat it.
A team of scientists from the Mayo Clinic (Rochester, MN, USA) retrieved formalin-fixed, paraffin-embedded tumor blocks and histological sections of SNS biopsied or resected between 1956 and 2013 for 25 tumors, including a second sample that was also characterized at the cytogenetic level. A frozen tumor sample was obtained from a single specimen characterized at the cytogenetic level. Formalin-fixed, paraffin-embedded material from 145 nonrelated tumors and normal tissues was also retrieved.
Transcriptome sequencing was performed on extracted ribonucleic acid (RNA), and the concentration was measured using a Qubit 2.0 Fluorometer (Life Technologies, Carlsbad, CA, USA). Paired-end 50-base transcriptome sequencing was performed using a HiSeq 2000 sequencer (Illumina, San Diego, CA, USA). Real-time polymerase chain reaction were carried out on extracted RNA and sequenced with a 3730xl DNA Analyzer (Applied Biosystems, Foster City, CA, USA). Other techniques including immunoblotting and immunofluorescence, luciferase assays immunohistochemistry, and fluorescence based in situ hybridization (FISH), were also used.
The scientists discovered a recurrent chromosomal translocation in SNS, t(2;4)(q35;q31.1), resulting in a paired box 3- mastermind-like 3 (PAX3-MAML3) fusion protein that is a potent transcriptional activator of PAX3 response elements. FISH and RT-PCR studies confirmed rearrangement of the PAX3 locus in 24 of 25 SNS tumors (96%) and identified the PAX3-MAML3 fusion gene in 19 of these tumors (79%). Five of the remaining SNS tumors exhibited rearrangement of the PAX3 locus without MAML3 involvement, and a single tumor showed rearrangement of the MAML3 locus without PAX3 involvement. They did not detect the PAX3-MAML3 fusion in 118 other tumors, including rhabdomyosarcomas, melanomas, and benign and malignant nerve sheath tumors or in 18 normal tissues, including 13 normal sinonasal tissues.
André M Oliveira, MD, the senior author of the study said, “It's unusual that a condition or disease is recognized, subsequently studied in numerous patients, and then genetically characterized all at one place. Usually these things happen over a longer period of time and involve separate investigators and institutions. Because of Mayo's network of experts, patient referrals, electronic records, biorepositories and research scientists, it all happened here. And this is only the tip of the iceberg. Who knows what is in our repositories waiting to be discovered?” The study was published on May 25, 2014, in the journal Nature Genetics.
Related Links:
Mayo Clinic
Life Technologies
Applied Biosystems
The cancer, that appears to be most common in women, starts in the nose and can spread to the rest of the face, meaning the patient will need disfiguring surgery in order to survive, but by uncovering the molecular makeup of the tumor it was found that many existing cancer drugs that could be used to treat it.
A team of scientists from the Mayo Clinic (Rochester, MN, USA) retrieved formalin-fixed, paraffin-embedded tumor blocks and histological sections of SNS biopsied or resected between 1956 and 2013 for 25 tumors, including a second sample that was also characterized at the cytogenetic level. A frozen tumor sample was obtained from a single specimen characterized at the cytogenetic level. Formalin-fixed, paraffin-embedded material from 145 nonrelated tumors and normal tissues was also retrieved.
Transcriptome sequencing was performed on extracted ribonucleic acid (RNA), and the concentration was measured using a Qubit 2.0 Fluorometer (Life Technologies, Carlsbad, CA, USA). Paired-end 50-base transcriptome sequencing was performed using a HiSeq 2000 sequencer (Illumina, San Diego, CA, USA). Real-time polymerase chain reaction were carried out on extracted RNA and sequenced with a 3730xl DNA Analyzer (Applied Biosystems, Foster City, CA, USA). Other techniques including immunoblotting and immunofluorescence, luciferase assays immunohistochemistry, and fluorescence based in situ hybridization (FISH), were also used.
The scientists discovered a recurrent chromosomal translocation in SNS, t(2;4)(q35;q31.1), resulting in a paired box 3- mastermind-like 3 (PAX3-MAML3) fusion protein that is a potent transcriptional activator of PAX3 response elements. FISH and RT-PCR studies confirmed rearrangement of the PAX3 locus in 24 of 25 SNS tumors (96%) and identified the PAX3-MAML3 fusion gene in 19 of these tumors (79%). Five of the remaining SNS tumors exhibited rearrangement of the PAX3 locus without MAML3 involvement, and a single tumor showed rearrangement of the MAML3 locus without PAX3 involvement. They did not detect the PAX3-MAML3 fusion in 118 other tumors, including rhabdomyosarcomas, melanomas, and benign and malignant nerve sheath tumors or in 18 normal tissues, including 13 normal sinonasal tissues.
André M Oliveira, MD, the senior author of the study said, “It's unusual that a condition or disease is recognized, subsequently studied in numerous patients, and then genetically characterized all at one place. Usually these things happen over a longer period of time and involve separate investigators and institutions. Because of Mayo's network of experts, patient referrals, electronic records, biorepositories and research scientists, it all happened here. And this is only the tip of the iceberg. Who knows what is in our repositories waiting to be discovered?” The study was published on May 25, 2014, in the journal Nature Genetics.
Related Links:
Mayo Clinic
Life Technologies
Applied Biosystems
Latest Pathology News
- Hyperspectral Dark-Field Microscopy Enables Rapid and Accurate Identification of Cancerous Tissues
- AI Advancements Enable Leap into 3D Pathology
- New Blood Test Device Modeled on Leeches to Help Diagnose Malaria
- Robotic Blood Drawing Device to Revolutionize Sample Collection for Diagnostic Testing
- Use of DICOM Images for Pathology Diagnostics Marks Significant Step towards Standardization
- First of Its Kind Universal Tool to Revolutionize Sample Collection for Diagnostic Tests
- AI-Powered Digital Imaging System to Revolutionize Cancer Diagnosis
- New Mycobacterium Tuberculosis Panel to Support Real-Time Surveillance and Combat Antimicrobial Resistance
- New Method Offers Sustainable Approach to Universal Metabolic Cancer Diagnosis
- Spatial Tissue Analysis Identifies Patterns Associated With Ovarian Cancer Relapse
- Unique Hand-Warming Technology Supports High-Quality Fingertip Blood Sample Collection
- Image-Based AI Shows Promise for Parasite Detection in Digitized Stool Samples
- Deep Learning Powered AI Algorithms Improve Skin Cancer Diagnostic Accuracy
- Microfluidic Device for Cancer Detection Precisely Separates Tumor Entities
- Virtual Skin Biopsy Determines Presence of Cancerous Cells
- AI Detects Viable Tumor Cells for Accurate Bone Cancer Prognoses Post Chemotherapy