New Study Explores the Use of Focused Ultradeep DNA Sequencing to Quantify Skin Cancer Risk
Recent research has shed new light on the carcinogenic effect of exposure to ultraviolet (UV) radiation, laying the groundwork for improvements in skin cancer risk stratification and prevention. A study published by Lei Wei, PhD, and colleagues in Science Advances detailed a method to measure the...
Multiancestry Meta-analysis of Prostate Cancer Genetics
A research team has published findings from a study that brought together data from genomic prostate cancer studies. Including more than 200,000 men of European, African, Asian, and Hispanic ancestry from around the world, the study is reportedly the largest, most diverse genetic analysis ever...
Germline-Somatic Interactions in Advanced Urothelial Cancer and Their Role in Disease Progression
In a study reported in Nature Communications, Bishoy M. Faltas, MD, of the Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, and colleagues identified common germline-somatic variant interactions in advanced urothelial cancer, with these...
Identifying Multiple Myeloma Prognostic Subgroups With Distinct Genetic and Clinical Features
Multiple myeloma is the second most common blood cancer, after non-Hodgkin lymphoma, diagnosed in the United States. In 2020, it is estimated that about 32,270 people will be diagnosed with the cancer, and despite advances in more effective treatments, nearly 13,000 will die of the disease.1...
Joyce V. Lee, PhD, on Triple-Negative Breast Cancer: MYC as a Predictor of Treatment Response
Joyce V. Lee, PhD, of the University of California, San Francisco, discusses data that suggest the MYC oncogene may indicate whether a patient with triple-negative breast cancer will respond to immunotherapy. Dr. Lee’s study is the first to describe MYC downregulation of MHC-I and to demonstrate translatable approaches that may overcome immune evasion (Abstract GS1-08).
Spectrum of Germline-Somatic Interactions in Advanced Urothelial Cancer
In a study reported in Nature Communications, Vosoughi et al identified common germline-somatic variant interactions in advanced urothelial cancer, with these interactions appearing to play a central role in disease progression. As stated by the investigators, “The prevalence and the biologic...
Interference of Clonal Hematopoiesis in DNA Repair Genes With Prostate Cancer Plasma Cell-Free DNA Testing
In a study reported in JAMA Oncology, Jensen and colleagues found that clonal hematopoiesis of indeterminate potential (CHIP) involving DNA repair genes can interfere with prostate cancer plasma cell-free DNA testing used to determine eligibility for poly (ADP-ribose) polymerase (PARP) inhibitor...
ASH 2020: Early Signs of Risk for Myeloproliferative Neoplasms May Appear in Childhood or in Utero
Genetic mutations linked to myeloproliferative neoplasms may emerge in childhood or even in utero, decades before they cause cancer, according to a late-breaking abstract presented today at the 2020 American Society of Hematology (ASH) Annual Meeting & Exposition by Jyoti Nangalia, MBBChir, and ...
Jyoti Nangalia, MBBChir, on MPN: A New Paradigm for the Development of Blood Cancer?
Jyoti Nangalia, MBBChir, of Wellcome Sanger Institute and the University of Cambridge, discusses how her team used large-scale whole-genome sequencing to precisely time the origins of a blood cancer and measure how it grew. The information could provide opportunities for early diagnosis and intervention (Abstract LBA-1).
ASH 2020: Multiple Myeloma Patient Similarity Network Identifies Prognostic Subgroups With Distinct Genetic and Clinical Features
An analysis by Bhalla et al of multiomics data from newly diagnosed patients with multiple myeloma has identified 3 main patient groups and 12 prognostic subgroups (as well as potential vulnerabilities in each subgroup) based on five data types generated from genomic and transcriptomic patient...
Study Shows Regional Variation in Genomic Testing for Men With Prostate Cancer
A study published by Michael S. Leapman, MD, and colleagues in JAMA Oncology found substantial regional variation in the use of genomic testing for prostate cancer, raising questions about access and other factors that might promote rapid adoption of new cancer technologies. “Little was known...
Native American Ancestry May Impact Somatic Alterations Among Latin American Patients With Lung Cancer
A research brief by Carrot-Zhang et al published in Cancer Discovery investigating inherited lung cancer risk—especially in nonsmokers—in Latin America has found that independent of smoking status, variation in EGFR and KRAS mutation frequency in Latin American patients with lung cancer was...
Trends in Positive BRCA Test Results Among Women Aged 65 and Older in the United States
In a study reported in JAMA Network Open, Guo et al found that the proportion of positive BRCA genetic test results markedly declined between 2008 and 2018 among women aged ≥ 65 years in the United States, with the trend likely reflecting what the investigators call a loosening of testing criteria...
Analysis Seeks to Identify Characteristics of 'Exceptional Responders' to Cancer Therapy
In a comprehensive analysis of patients with cancer who had exceptional responses to therapy, researchers identified molecular changes in the patients’ tumors that may explain some of these outcomes. The results, published by Wheeler et al in Cancer Cell, demonstrated that genomic characterizations ...
Screening Younger Women for Variants Linked to Breast and Ovarian Cancers May Be Cost-Effective
Population-wide screening for genetic variants linked to hereditary breast and ovarian cancers may be cost-effective in women between the ages of 20 and 35, according to a study published by Guzauskas et al in JAMA Network Open. However, screening for older women was not cost-effective, the...
Paclitaxel Plus Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer: Long-Term Follow-up and Genomic Analysis
In a 7-year follow-up of the phase III CALGB 40601/Alliance neoadjuvant trial reported in the Journal of Clinical Oncology, Fernandez-Martinez et al found that paclitaxel combined with trastuzumab/lapatinib was associated with improved survival outcomes vs paclitaxel/trastuzumab in women with...
FDA Expands Approval of Companion Diagnostic for Olaparib in Prostate Cancer
On November 9, the U.S. Food and Drug Administration (FDA) approved FoundationOne Liquid CDx to be used as a companion diagnostic for olaparib. As a companion diagnostic, FoundationOne Liquid CDx will use a blood-based biopsy to identify patients with BRCA1, BRCA2, and/or ATM alterations and...
Olaparib for Patients With Metastatic Breast Cancer and Mutations in Homologous Recombination–Related Genes
In a phase II Translational Breast Cancer Research Consortium (TBCRC) study (TBCRC 048; Olaparib Expanded) reported in the Journal of Clinical Oncology, Nadine M. Tung, MD, and colleagues found that olaparib produced high response rates in patients with metastatic breast cancer and germline PALB2...
Study Identifies Genetic Variants Linked to Bevacizumab-Induced Adverse Events
Researchers have found two common genetic variants that may be used to predict whether patients with cancer may have severe adverse events when treated with the anti-VEGF monoclonal antibody bevacizumab. A genome-wide association study—according to researchers, the largest such study in patients...
Study Finds Universal Genetic Testing Uncovers More Inherited Mutations vs Guideline-Based Genetic Testing
Universal genetic testing may uncover inherited genetic mutations, and could individualize cancer therapies, improve survival, and strengthen the use of precision medicine. In a new study published by N. Jewel Samadder, MD, and colleagues in JAMA Oncology, researchers conducted genetic testing in...
Study Finds Distinct Genomic Alterations May Contribute to More Aggressive Prostate Cancer in Black Men
A study by Liu et al published in Molecular Cancer Research investigated why Black men appear to be more likely to develop aggressive prostate cancer than White men. Researchers found that prostate tumors in Black men had higher frequencies of distinct genetic alterations, which may contribute to...
Breast Cancer Risk and Disease-Causing Genetic Mutations in Women Older Than 65
Women with breast cancer onset after age 65 often do not qualify for genetic testing, yet little is known about the frequency of disease-causing mutations in breast cancer predisposition genes in this population. In a new study, researchers investigated the prevalence of disease-causing variants in ...
Next-Generation BRAF Inhibitor Shows Activity in Phase I/II Trial
A new drug designed to treat cancers in patients with an altered BRAF gene showed activity and had a favorable safety profile in an early-phase trial. These findings were presented by Janku et al at the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (Abstract LBA-05)....
FDA Approves Companion Diagnostic for Three Targeted Therapies for Advanced Ovarian, Breast, and Non–Small Cell Lung Cancers
On October 27, the U.S. Food and Drug Administration (FDA) approved the FoundationOne Liquid CDx test for three new companion diagnostic indications to help match patients who may benefit from treatment with specific FDA-approved targeted therapies. The new indications are for alpelisib (Piqray) in ...
Targeted Inhibitor of Mutant KRAS Gene Shows Activity in Early Trial
Adagrasib (MRTX849), a novel agent that targets a mutated form of the KRAS gene—the most commonly altered oncogene in human cancers, and one long considered “undruggable”—caused tumor shrinkage in most patients in a clinical trial, with manageable side effects, researchers reported at the 32nd...
Companion Diagnostic to Identify NTRK Fusions in Patients With Solid Tumors Eligible for Treatment With Larotrectinib Approved by the FDA
On October 23, the U.S. Food and Drug Administration (FDA) approved the next-generation sequencing–based FoundationOne CDx test as a companion diagnostic to identify fusions in the neurotrophic receptor tyrosine kinase (NTRK) genes NTRK1, NTRK2, and NTRK3 in DNA isolated from tumor tissue specimens ...
FDA Pipeline: Priority Reviews in EGFR-Mutant Lung Cancer, Advanced Renal Cell Carcinoma; Fast Track Designations in CLL and Solid Tumors
Recently, the U.S. Food and Drug Administration (FDA) granted Priority Review to treatments for EGFR-mutant lung cancer and advanced renal cell carcinoma; granted Fast Track designation to agents in chronic lymphocytic leukemia (CLL) and locally advanced or metastatic solid tumors; and more....
Radiation-Induced Genetic Deletions May Be Associated With Poorer Patient Outcomes
Treatment of diffuse gliomas with radiotherapy resulted in an increased number of genomic small deletions that make up a unique signature, according to findings presented at the Molecular Analysis for Precision Oncology (MAP) Congress 2020 (Abstract 2MO). Furthermore, an increased burden of...
Do Patients With Early-Stage NSCLC Have a Higher Tumor Mutational Burden Than Those With More Advanced Disease?
The tumors of patients with stage I and II non–small cell lung cancer (NSCLC) demonstrated a generally higher tumor mutational burden and more often displayed the mutational signature associated with tobacco smoking than those of patients with more advanced disease, according to findings presented...
Fragment Analysis as a MET Exon 14 Screening Strategy in NSCLC Tumors
Comparison of two techniques used in screening non–small cell lung cancer (NSCLC) tumor samples demonstrated that fragment analysis could detect large MET exon 14 skipping deletions that were missed by next-generation sequencing, according to findings presented at the Molecular Analysis for...
Molecular Profiles and Actionable Alterations Identified in the NCI-MATCH Trial
In a report in the Journal of Clinical Oncology, Keith T. Flaherty, MD, and colleagues describe the current status of and findings from the ongoing NCI-MATCH (National Cancer Institute Molecular Analysis for Therapy Choice) trial. The aim of the trial is to determine the likelihood of identifying...
Trends to Watch in Early-Onset Cancer Among Young Adults
Although cancer incidence and mortality rates for all cancers combined are considerably lower in younger adults than older adults, a disturbing pattern is beginning to emerge in the development of early-onset cancers, typically diagnosed in older patients, occurring in younger adults. The rising...
Cancer Therapy Based on Molecular Tumor Board Recommendations: Improvement in Outcomes?
Patients receiving care for advanced cancer based on the recommendations of a molecular tumor board were more likely to survive or experience a longer period without disease progression, according to results from a study published by Kato et al in Nature Communications. Razelle Kurzrock, MD,...
Pilot Study Finds Liquid Biopsy Delivers Results Faster Than Tissue Biopsy
A pilot study comparing liquid biopsy with tissue-based testing showed that liquid biopsy delivered results approximately 10 days faster than tissue biopsy, according to research presented by Nir Peled, MD, PhD, and colleagues at the International Association for the Study of Lung Cancer (IASLC)...
Liquid Biopsy May Be a Timely and Effective Testing Method for Patients With NSCLC: Findings From Canada
Next-generation sequencing of cell-free DNA (cfDNA) obtained from blood samples may improve diagnostic testing in patients with advanced non–small cell lung cancer (NSCLC) and may also be faster and less expensive than standard tissue profiling, according to research presented by Natasha B. Leighl, ...
Genetic Testing May Be Cost-Effective for Newly Diagnosed Patients With GIST
In a paper published by Banerjee et al in JAMA Network Open, researchers reported that genetic testing is cost-effective and beneficial for newly diagnosed patients with metastatic gastrointestinal stromal tumors (GIST), a type of soft-tissue sarcoma that develops in specialized nerve cells in the...
Is ctDNA Effective in Detecting Genomic Alterations in Patients With Metastatic Kidney Cancer?
Circulating tumor DNA (ctDNA) analysis is a minimally invasive genomic assessment tool utilizing targeted next-generation sequencing of peripheral blood. At the ESMO Virtual Congress 2020, Zengin et al reported genomic results from a large cohort of patients with metastatic renal cell carcinoma...
Nivolumab Shows Activity in edPOLE-Mutated, MMR-Proficient Advanced Cancers
Nivolumab monotherapy showed high response and disease control rates in patients with pathogenic exonuclease domain POLE (edPOLE)-mutated, mismatch repair (MMR)-proficient advanced tumors containing confirmed pathogenic mutations, according to findings presented by Benoit J.C. Rousseau, MD, PhD, of ...
Use of ctDNA to Direct Therapy in Advanced Breast Cancer
In the phase IIa plasmaMATCH platform trial reported in The Lancet Oncology, Nicholas C. Turner, MD, and colleagues found that circulating tumor DNA (ctDNA) provided accurate genotyping that permitted selection of directed therapies in patients with advanced breast cancer. Study Details The...
Role of Inherited GATA3 Variant in Response to Treatment, Disease Relapse in Pediatric ALL
Research published by Zhang et al in the Journal of the National Cancer Institute showed that an inherited variation in the GATA3 gene strongly influences early response to chemotherapy and is linked to relapse in children with acute lymphoblastic leukemia (ALL). Minimal residual disease (MRD)...
Racial Differences in Genomic Profiles of Primary and Metastatic Prostate Cancer
In a letter to the editor published in The New England Journal of Medicine, Brandon A. Mahal, MD, and colleagues described genomic differences in prostate cancer in Black, White, and Asian men. Study Details The study involved next-generation sequencing data from patients who had been treated for...
Phase II Trial of Capmatinib for MET Exon 14–Mutated or MET-Amplified Advanced NSCLC
As reported in The New England Journal of Medicine by Wolf et al, the phase II GEOMETRY mono-1 trial has shown durable responses with the selective MET inhibitor capmatinib in patients with advanced non–small cell lung cancer (NSCLC) and MET exon 14–skipping mutations. The trial supported the May...
At Last: Targeting KRAS-Mutated Tumors ‘Is Now a Reality’
KRAS G12C inhibitors—which at this point include AMG 510 (now labeled sotorasib) and MRTX849—are proving to be active in KRAS G12C–mutated tumors, especially non–small cell lung cancer (NSCLC). KRAS G12C is a newly “druggable” target, joining what is still a limited list of some 3,000 potential...
PORTEC-3: Effect of Molecular Classification of Endometrial Cancer on Outcomes With Adjuvant Therapy
In a study reported in the Journal of Clinical Oncology, Alicia Léon-Castillo, MD, of Leiden University Medical Center, the Netherlands, and colleagues identified outcomes associated with molecular subgroups of patients with high-risk endometrial cancer enrolled in the PORTEC-3 trial of adjuvant...
FDA Approves FoundationOne Liquid CDx, a Pan-Tumor Liquid Biopsy Test
On August 28, the U.S. Food and Drug Administration (FDA) approved FoundationOne Liquid CDx, a comprehensive pan-tumor liquid biopsy test for patients with solid tumors. FoundationOne Liquid CDx is a comprehensive genomic-profiling test that analyzes more than 300 cancer-related genes and multiple...
Three Novel Genetic Variants Linked to Male Breast Cancer Discovered
Scientists have newly discovered three genetic changes that increase the risk of breast cancer in men. These findings were published by Maguire et al in the Journal of the National Cancer Institute. The researchers identified three common variations in DNA that predispose men to developing breast...
Dabrafenib Plus Trametinib in BRAF V600E–Mutated Tumors: NCI-MATCH Subprotocol H
As reported in the Journal of Clinical Oncology by Salama et al, the NCI-MATCH trial subprotocol H (EAY131-H) has shown durable responses with dabrafenib plus trametinib in previously treated patients with BRAF V600E–mutant tumors. Study Details The study enrolled 35 patients with mixed-histology...
Molecular Testing in Metastatic Colorectal Cancer: Understanding How, When, and What to Profile
“In line with the emergence of targeted therapies, molecular biomarker testing in metastatic colorectal cancer has evolved over the past decade,” noted Jeanne Tie, MD, MBChB, FRACP, who acknowledged there is confusion about the best ways to use molecular testing in the clinic. Dr. Tie, who is...
FDA Pipeline: Approval for First Liquid Biopsy Next-Generation Sequencing Companion Diagnostic; Designations in Ovarian Cancer, Leukemia, and Lymphoma
Recently, the U.S. Food and Drug Administration (FDA) approved the first liquid biopsy companion diagnostic that also uses next-generation sequencing technology to identify patients with non–small cell lung cancer (NSCLC) and specific types of EGFR mutations. The FDA also granted Fast Track...
CICERO Software May Enable Detection of Cancer-Causing Gene Fusions
After years of development, engineering, and enhancement, researchers at St. Jude Children’s Research Hospital in Memphis have made available a software system that enables better detection of gene fusions. The system, called CICERO, offers additional insights into cancers as well as new targets...
