November 2018—Common genetic variants contribute to risk of rare severe neurodevelopmental disorders: The traditional paradigm broadly classifies genetic diseases into rare disorders caused by a single gene variant and common disorders caused by complex interplay among multiple genes. However, recent research has shown that penetrance and disease phenotype, even in disorders thought to be monogenic, are affected by common genetic variation.Read More »
Cell-free DNA tumor mutational burden predicts efficacy of immune checkpoint inhibitors October 2018—Immune checkpoint inhibitors have emerged as a potent class of therapy for a variety of malignancies. The biologic rationale for these drugs is that somatic mutations, not necessarily in cancer driver genes, may accumulate in tumor cells, resulting in amino acid changes that create neoantigens (epitopes not present in normal cells during maturation of the immune system).Read More »
Ability of genetic alterations to predict development of acute myeloid leukemia
September 2018—Acute myeloid leukemia affects more than 60,000 people in the United States every year and has a mortality rate of more than 90 percent. It is the most common form of acute leukemia and is caused by unchecked growth of immature precursor cells in the bone marrow. These immature cells, or blasts, are myeloid precursors that often develop into dysfunctional, cancerous white blood cells that fill the bone marrow and spread into the blood.
Prevalence of clonal hematopoiesis mutations in tumor-only clinical genomic profiling of solid tumors
August 2018—Challenges to implementing next-generation sequencing-based comprehensive molecular profiling of solid tumors include reliably separating germline variants from somatic variants. This is an important consideration, particularly when a “tumor-only” profiling approach is used.
July 2018—Correlation between tumor mutation burden and efficacy of combination immunotherapy in nonsmall cell lung cancer: Checkpoint inhibitor therapy has dramatically improved outcomes in many cancer types, with treatments including antibodies against cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), programmed cell death receptor-1 (PD-1), and its ligand (PD-L1).Read More »
June 2018—Genetics and pathogenesis of diffuse large B-cell lymphoma: Understanding the genetic basis of diffuse large B-cell lymphoma is important for understanding the pathogenesis of the disease and the molecular attributes that may influence therapeutic response.Read More »
May 2018—DNA methylation-based testing to classify central nervous system tumors: Despite being the mainstay of pathology tissue diagnostics, microscope-based histological review has limitations. Among them is that pathologists may have differing opinions about a case. This interobserver variability may result in over- or undertreatment of the patient and lack of agreement about which diagnosis is correct.Read More »
April 2018—Effect of inherited TP53 mutations on children with B-cell ALL: TP53 has been referred to as the “guardian of the genome” because it plays a central role in regulation of the cell cycle, DNA repair, and apoptosis, and because somatic mutations in TP53 are frequently identified in many tumor types.Read More »
March 2018—Nonendoscopic detection of Barrett’s esophagus using DNA methylation biomarkers: Esophageal adenocarcinoma is an aggressive disease, with a less than 20 percent five-year survival rate, and its incidence is rapidly increasing. Early detection of esophageal adenocarcinoma or its precursor lesion, Barrett’s esophagus, would enable more effective treatment strategies and a greater chance of cure.Read More »
February 2018—Gene expression and risk of leukemic transformation in myelodysplasia: The myelodysplastic syndromes represent a group of clonal hematopoietic disorders with varying prognoses, with survival ranging from a few months to more than 10 years. Multiple laboratory measurements have been used in attempts to provide reliable prognostic assessments, including bone marrow blast counts, severity of peripheral cytopenia, cytogenetic findings, and, most recently, gene-mutation profiling.Read More »