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Genomics/Genetics

Research Examines a New Tool for Discovering Cancer-Driving Structural Variations

An advanced software tool for analyzing DNA sequences from tumor samples has uncovered new, likely cancer-driving genes. In a study, Weill Cornell Medicine researchers designed the software, known as CSVDriver, to map and analyze the locations of large mutations, known as structural variants, in...

CNS Cancers
Genomics/Genetics

Researchers Identify Potential Biomarker to Distinguish Group 3 and Group 4 Medulloblastomas

It may soon be possible to identify group 4 medulloblastomas from more aggressive group 3 tumors. Research based on a little-explored part of RNA that creates proteins may lead to the development of better-targeted therapies, according to investigators at the Johns Hopkins Kimmel Cancer Center....

Genomics/Genetics

Tissue vs ctDNA NGS for Detecting Actionable Alterations in Patients With Advanced Cancer

A large prospective analysis, published by Bayle et al in Annals of Oncology, evaluated differences between tissue and circulating tumor DNA (ctDNA) next-generation sequencing (NGS) with a large cancer gene panel. The investigators compared the impacts of both methods in terms of molecular tumor...

Gastroesophageal Cancer
Genomics/Genetics

Genetic Variation May Explain Racial Disparity in Esophageal Cancer Cases

Esophageal adenocarcinoma is a type of cancer affecting the mucus-secreting glands of the lower esophagus and is the most common form of esophageal cancer. It is often preceded by Barrett’s metaplasia, a deleterious change in cells lining the esophagus. Though the cause of esophageal adenocarcinoma ...

Breast Cancer
Gynecologic Cancers
Genomics/Genetics

Constitutional BRCA1 Methylation and Risk of Triple-Negative Breast Cancer and Ovarian Cancer

In a case-control study within the U.S. Women’s Health Initiative (WHI) study population reported in JAMA Oncology, Lønning et al found that BRCA1 promoter methylation identified in white blood cells was associated with increased risks of incident triple-negative breast cancer and high-grade serous ...

Genomics/Genetics

Cancer Phenotypes Associated With Germline CHEK2 Variants

In a retrospective cohort study reported in JAMA Oncology, Brittany L. Bychkovsky, MD, MSc, and colleagues analyzed the spectrum of cancer phenotypes associated with germline CHEK2 variants. They found that CHEK2 pathogenic variants apart from p.I157T, p.S428F, and p.T476M were associated with...

Prostate Cancer
Genomics/Genetics

Genomic Testing May Aid in Identifying Patients of African Descent With High-Risk Prostate Cancer

Black patients of African descent tend to be diagnosed more frequently with prostate cancer and have higher mortality rates than patients of other races and ethnicities. Despite this substantial disparity, few prospective studies focused on maximizing the recruitment of African American patients...

Solid Tumors
Genomics/Genetics

Selpercatinib in RET Fusion–Positive Solid Tumors Other Than Lung or Thyroid Malignancies

As reported in The Lancet Oncology by Vivek Subbiah, MD, and colleagues, the phase I/II LIBRETTO-001 basket trial has shown that the RET kinase inhibitor selpercatinib demonstrated activity in patients with RET fusion–positive solid tumors in an analysis excluding lung and thyroid cancers. Findings ...

Genomics/Genetics

Selpercatinib Approved for Locally Advanced or Metastatic RET Fusion–Positive Solid Tumors

On September 21, the U.S. Food and Drug Administration (FDA) granted accelerated approval to selpercatinib (Retevmo) for adult patients with locally advanced or metastatic solid tumors with a rearranged during transfection (RET) gene fusion and disease progression on or following prior systemic...

Lung Cancer
Genomics/Genetics

FDA Approves Selpercatinib for Locally Advanced or Metastatic RET Fusion–Positive NSCLC

On September 21, the U.S. Food and Drug Administration (FDA) granted regular approval to selpercatinib (Retevmo) for adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with a RET gene fusion (as detected by an FDA-approved test). The FDA also approved the Oncomine ...

Colorectal Cancer
Genomics/Genetics

ctDNA Analysis of Acquired EGFR Resistance Alterations With First-Line Cetuximab Plus Chemotherapy in Patients With Metastatic Colorectal Cancer

In a circulating tumor DNA (ctDNA) substudy from the CALGB/SWOG-80405/Alliance trial reported in the Journal of Clinical Oncology, Kanwal Raghav, MD, MBBS, and colleagues found that first-line use of the anti-EGFR antibody cetuximab combined with chemotherapy was associated with only a small number ...

Prostate Cancer
Genomics/Genetics

Prostate Tumor Biology May Be Influenced by Genetic Ancestry

Certain genetic variants found in prostate tumors of men of African descent were associated with African ancestry, according to two studies presented at the 15th American Association for Cancer Research (AACR) Conference on the Science of Cancer Health Disparities in Racial and Ethnic Minorities...

Colorectal Cancer
Genomics/Genetics

Acquired EGFR Inhibitor Resistance Alterations Identified in ctDNA Analysis in Patients With Refractory Metastatic Colorectal Cancer

In a study reported in the Journal of Clinical Oncology by Topham et al, circulating tumor DNA (ctDNA) analysis indicated significantly increased frequencies of multiple potential EGFR inhibitor resistance alterations among patients with refractory metastatic colorectal cancer with vs without prior ...

Lung Cancer
Genomics/Genetics

Updated Results From the ADAURA Trial of Adjuvant Osimertinib in EGFR-Mutated NSCLC

Newly released results from the phase III ADAURA trial revealed that osimertinib yielded a 5.5-year median disease-free survival in the postsurgical treatment of patients with EGFR-mutated non­–small cell lung cancer (NSCLC), and nearly three in four patients treated with adjuvant osimertinib were...

breast cancer
genomics/genetics

Antonio Marra, MD, on Metastatic Breast Cancer: Patterns of Genomic Instability and Their Effect on Treatment

Antonio Marra, MD, of Memorial Sloan Kettering Cancer Center, discusses a mutational signature analysis that reveals patterns of genomic instability linked to resistance to endocrine therapy with or without CDK4/6 inhibition in patients with estrogen receptor–positive/HER2-negative metastatic breast cancer (Abstract 210O).

Lung Cancer
Genomics/Genetics

Researchers Examine How Air Pollution May Drive Lung Cancer in Never-Smokers

A new mechanism has been identified through which very small pollutant particles in the air may trigger lung cancer in people who have never smoked, paving the way to new prevention approaches and the development of novel therapies, according to late-breaking data reported by Charles Swanton, MBBS, ...

Lung Cancer
Genomics/Genetics
Immunotherapy

Addition of Sintilimab and Bevacizumab Biosimilar to Chemotherapy for Patients With Advanced EGFR-Mutated NSCLC and Disease Progression on EGFR Inhibitors

In an interim analysis of the Chinese phase III ORIENT-31 trial reported in The Lancet Oncology, Lu et al found that the addition of sintilimab and the bevacizumab biosimilar IBI305 to chemotherapy prolonged progression-free survival in patients with advanced EGFR-mutated nonsquamous non–small cell ...

Prostate Cancer
Genomics/Genetics

Two New Studies Find Aggressive Prostate Cancer May Be Linked to Ancestral Heritage

Two studies published simultaneously by Jaratlerdsiri et al in Nature and Gong et al in Genome Medicine have identified genetic signatures explaining ethnic differences in the severity of prostate cancer, particularly in sub-Saharan Africa. Through genetic sequencing of prostate cancer tumors from...

Hepatobiliary Cancer
Genomics/Genetics

Study Examines How Genetic Mutations May Contribute to the Development of Cholangiocarcinoma

A team of researchers from the University of Rochester discovered how certain genetic mutations fuel the growth of cholangiocarcinoma, a rare but aggressive type of malignancy that has been on the rise in the United States. Their work, published by Guo et al in Cell Reports this week, details the...

CNS Cancers
Genomics/Genetics

ASTRO Issues Clinical Guideline on Radiation Therapy for IDH-Mutant Glioma

A new clinical guideline from the American Society for Radiation Oncology (ASTRO) provides recommendations on the use of radiation therapy to treat patients with isocitrate dehydrogenase (IDH)-mutant grade 2 and grade 3 diffuse glioma. Evidence-based recommendations outline the multidisciplinary...

Thyroid Cancer
Genomics/Genetics

Expert Point of View: Alexander T. Pearson, MD, PhD

Alexander T. Pearson, MD, PhD, Assistant Professor of Medicine at the University of Chicago, commended the artificial intelligence (AI)-augmented, ultrasound-based platform for screening and staging of thyroid cancer.  “In this study, Dr. Chan and colleagues processed high-resolution ultrasound...

Thyroid Cancer
Genomics/Genetics

Study Finds AI Ultrasound Platform Can Predict Thyroid Malignancy, Pathologic Stage, and BRAF Mutation Status

An artificial intelligence (AI) ultrasound platform that incorporates multiple methods of machine learning can accurately predict thyroid malignancy as well as pathologic and genomic outcomes, according to data presented at the 2022 Multidisciplinary Head and Neck Cancers Symposium.1 Findings from...

Lung Cancer
Genomics/Genetics

Addition of Chemotherapy to Gefitinib in First-Line Treatment of Advanced NSCLC With EGFR Mutations

In an updated analysis of the Japanese phase III NEJ009 trial reported in the Journal of Clinical Oncology, Miyauchi et al found that gefitinib plus carboplatin/pemetrexed was associated with prolonged progression-free survival and progression-free survival 2—but loss of significance in overall...

Breast Cancer
Genomics/Genetics

Researchers Identify Markers of Chemotherapy Resistance and Outcome in Patients With Triple-Negative Breast Cancer

Researchers have identified biological markers in patients with triple-negative breast cancer that are associated with resistance to chemotherapy. The study was published by Anurag et al in the journal Cancer Discovery and was funded by the National Cancer Institute’s Clinical Proteomics Tumor...

Genomics/Genetics

PREMMplus Tool May Assist in Identifying People Likely to Benefit From Multigene Hereditary Cancer Risk Assessment

An online tool developed by researchers and physicians at Dana-Farber Cancer Institute may accurately and rapidly identify people who should undergo testing for inherited genetic changes that raise the risk of developing certain cancers, according to findings reported by Yurgelun et al in the...

Genomics/Genetics

Pralsetinib Achieves Tissue-Agnostic Benefits for Patients With RET Fusion–Positive Cancers

The highly selective RET inhibitor pralsetinib was well tolerated and demonstrated robust, durable responses in patients with RET fusion–positive cancers regardless of tumor type, according to results from the international phase I/II ARROW trial. Results from the trial were published in Nature...

Lymphoma
Genomics/Genetics

Study Reveals Potential Genomic Contributors to the Development of DLBCL

By searching previously ignored regions of the genome, researchers have found a multitude of new genetic mutations that may contribute to diffuse large B-cell lymphoma (DLBCL). These findings were published by Bal et al in Nature. “Our findings not only show that these mutations can contribute to...

Leukemia
Genomics/Genetics

Molecular Map Reveals Insights Into the Genetic Drivers of CLL

A newly constructed map of the landscape of genetic changes in chronic lymphocytic leukemia (CLL) may provide a better understanding of this complex malignancy, which could lead to more accurate prognoses for patients, improved diagnostics, and novel treatments. These research findings were...

Lung Cancer
Genomics/Genetics

FDA Approves Capmatinib for Metastatic NSCLC With MET Exon 14 Skipping Mutations

On August 10, 2022, the U.S. Food and Drug Administration (FDA) granted regular approval to capmatinib (Tabrecta) for adult patients with metastatic non–small cell lung cancer (NSCLC) whose tumors have a mutation leading to mesenchymal-epithelial transition (MET) exon 14 skipping, as detected by an ...

Lung Cancer
Genomics/Genetics
Immunotherapy

Study Finds Adding Tremelimumab and Durvalumab to Chemotherapy Improves Overall Survival in Metastatic NSCLC Regardless of KRAS/STK11/KEAP1 Mutations

Patients with metastatic non–small cell lung cancer (NSCLC) who received a combined therapy of tremelimumab, durvalumab, and chemotherapy experienced longer overall survival compared with those who received chemotherapy alone, regardless of STK11, KEAP1, or KRAS mutational status. These findings...

Multiple Myeloma
Genomics/Genetics

Researchers Find Potential Link Between Genetic Mutations and Treatment Resistance in Patients With Relapsed or Refractory Multiple Myeloma

Researchers studying the molecular landscape of over 500 patients with relapsed or refractory multiple myeloma discovered a prevalence of activated key oncogenic pathways in these patients—much more than previously thought. Upward of 45% to 65% of NF-κB and RAS/MAPK pathways each had alterations....

Hepatobiliary Cancer
Genomics/Genetics

Study Sheds Light on Mechanisms Driving Cancer Induced by Organic Solvent Used in Printing Industry

1,2-Dichloropropane (1,2-DCP) is a synthetic organic solvent used in the printing industry. It was linked to cholangiocarcinoma in 2013, when printing company employees in Osaka, Japan, exposed to 1,2-DCP were diagnosed with the cancer. Thereafter, the International Agency for Research on Cancer...

CNS Cancers
Genomics/Genetics

Investigational Blood Test May Help Improve Diagnosis and Monitoring of Glioma

Researchers at Massachusetts General Hospital (MGH) who previously developed a blood test for mutations in a gene linked to gliomas have now applied their technology to detect additional mutations—in this case, in the gene that codes for the epidermal growth factor receptor (EGFR). The advance,...

Genomics/Genetics
Breast Cancer
Gynecologic Cancers

Does Disclosing Maternal Status Affect Children’s Health Behaviors?

Telling children about their mother’s risk of hereditary breast and/or ovarian cancer does not adversely influence the offspring’s lifestyle or quality of life in the long term, according to a new study published by McDonnell et al in the journal Pediatrics. The study looked at the mutation status...

CNS Cancers
Genomics/Genetics

Deciphering the Elusive Origin and Pathways of Brain Metastases

The effective treatment of patients with brain metastases is an unmet need because, until fairly recently, patients with brain metastases were excluded from clinical trials of systemic therapies. However, the emergence of molecular targeted therapies has allowed a new treatment approach in patients ...

CNS Cancers
Genomics/Genetics

Dual-Targeted Therapy Improves Outcomes vs Chemotherapy for Some Pediatric Patients With Low-Grade Glioma

The all-oral combination of dabrafenib plus trametinib—two targeted therapies—significantly improved the overall response rate vs standard-of-care chemotherapy with carboplatin plus vincristine in pediatric patients with BRAF V600 mutation–positive low-grade gliomas. The clinical benefit rate...

Pancreatic Cancer
Genomics/Genetics

Outcomes in Pancreatic Cancer Surveillance Program for Carriers of Germline CDKN2A Pathogenic Variants

In a Dutch study reported in the Journal of Clinical Oncology, Klatte et al provided findings from a 20-year follow-up of a pancreatic cancer surveillance program including carriers of germline CDKN2A pathogenic variants. Study Details The study included 347 carriers in the Netherlands who...

Solid Tumors
Genomics/Genetics

Dabrafenib/Trametinib Combination Receives FDA Approval for BRAF V600E–Mutated Solid Tumors

On June 23, the U.S. Food and Drug Administration (FDA) granted accelerated approval for dabrafenib (Tafinlar) plus trametinib (Mekinist) for the treatment of adult and pediatric patients aged 6 years and older with unresectable or metastatic solid tumors with a BRAF V600E mutation whose disease...

COVID-19
Colorectal Cancer
Survivorship
Genomics/Genetics

American Cancer Society Investigators Present Studies on COVID-19 Pandemic, Racial/Ethnic Disparities, and Coverage for Genomic Testing

Investigators at the American Cancer Society presented results of several studies during poster sessions at the 2022 ASCO Annual Meeting. Summaries of a few of these studies are provided here. COVID-19 and Cancer Mortality According to a new study led by researchers at the American Cancer Society,...

Pancreatic Cancer
Genomics/Genetics
Immunotherapy

NOTABLE Trial: Survival in Pancreatic KRAS Wild-Type Cancer Improved With Addition of Nimotuzumab to Gemcitabine

In patients with locally advanced or metastatic pancreatic cancer and KRAS wild-type tumors, novel treatment with the monoclonal antibody nimotuzumab, which targets the epidermal growth factor receptor (EGFR),  plus gemcitabine significantly improved overall survival and other outcomes over...

Gynecologic Cancers
Genomics/Genetics

Factors That May Predict Response to the Addition of Bevacizumab to Front-Line Chemotherapy in Patients With Endometrial Cancer

In an analysis from an NRG Oncology/Gynecologic Oncology Group phase II study (GOG-86P) reported in the Journal of Clinical Oncology, Thiel et al looked at outcomes in patients with advanced endometrial cancer treated with bevacizumab added to front-line chemotherapy. The investigators found that...

Multiple Myeloma
Genomics/Genetics

Study Identifies Three-Gene Signature That May Predict Response to Selinexor in Patients With Multiple Myeloma

Researchers have, for the first time, identified genes that may predict response to a therapy for a blood cancer that can have serious side effects for some patients. The therapy, selinexor, is part of the treatment armamentarium for multiple myeloma, but the ability to target its use to patients...

Genomics/Genetics

Germline Variants in Types of Cancer Without Hereditary Testing Guidelines

In a study reported in JAMA Network Open, Timothy A. Yap, MBBS, PhD, FRCP, and colleagues found that a substantial proportion of patients with cancer types that lacked hereditary testing guidelines harbored germline pathogenic/likely pathogenic variants. Study Details The study included data from...

lung cancer
genomics/genetics

Gilberto de Lima Lopes, Jr, MD, MBA, and Matthew Krebs, PhD, on NSCLC: Updated Results With Amivantamab-vmjw

Gilberto de Lima Lopes, Jr, MD, MBA, of the Sylvester Comprehensive Cancer Center at the University of Miami, and Matthew Krebs, PhD, of The University of Manchester and The Christie NHS Foundation Trust, discuss results from the CHRYSALIS study. The trial showed that the bispecific antibody amivantamab-vmjw demonstrated antitumor activity, even after prior treatment, in patients with non–small cell lung cancer that exhibits the MET exon 14 skipping mutation (Abstract 9008).

colorectal cancer
genomics/genetics

Michael J. Overman, MD, and Smitha Krishnamurthi, MD, on RAS Wild-Type Metastatic Colorectal Cancer: Refining Treatment Strategy

Michael J. Overman, MD, of The University of Texas MD Anderson Cancer Center, and Smitha Krishnamurthi, MD, of the Cleveland Clinic, review three abstracts, all of which enrolled patients with newly diagnosed RAS and BRAF wild-type metastatic colorectal cancer with left-sided primary tumors. The discussion centers on what the study results indicate about the use of an EGFR therapy and weighing the risk to quality of life from rash, in particular (Abstracts LBA3503, LBA3504, LBA3505).

Genomics/Genetics
Myelodysplastic Syndromes
Leukemia

Demethylation and Upregulation of the Oncogene SALL4 After Hypomethylating Therapy

In a study reported in The New England Journal of Medicine, Liu et al found that hypomethylating therapy was associated with upregulation of the oncogene SALL4 in a high proportion of patients with myelodysplastic syndrome. They also identified the gene region that is demethylated and responsible...

Leukemia
Genomics/Genetics

Triplet Combination Therapy Yields High Response Rates in Patients With FLT3-Mutated AML

FLT3-ITD–mutated acute myeloid leukemia (AML) is an aggressive disease usually resistant to available treatment options, resulting in high front-line response rates but short response durations and low survival rates. Quizartinib—a potent selective FLT3 inhibitor—can work synergistically with...

Genomics/Genetics
Bladder Cancer

Real-World Uptake of FGFR-Alteration Testing and Gene-Targeted Therapy for Patients With Urothelial Cancer

In a study reported in a research letter in JAMA Oncology, Nimgaonkar et al found that less than half of patients with urothelial cancer who had received first-line platinum-based therapy underwent testing for FGFR alterations and that less than half of patients with susceptible alterations...

Leukemia
Myelodysplastic Syndromes
Genomics/Genetics

Targeted Therapy Emavusertib Shows Activity in Patients With MDS or AML With Specific Mutations

Mutations in SF3B1 and U2AF1 can drive overexpression of activated IRAK4—which regulates inflammation and promotes cancer cell growth and survival—and are associated with a poor prognosis for patients with high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Emavusertib is a...

Prostate Cancer
Genomics/Genetics

Differences in Germline Variant Spectrum Between Black and White Men With Prostate Cancer

In a study presented at the 2022 ASCO Annual Meeting (Abstract 10502) and simultaneously published in JCO Precision Oncology, Veda N. Giri, MD, and colleagues found that Black men with prostate cancer exhibited a lower frequency and narrower spectrum of germline pathogenic or likely pathogenic...

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