Author
Jonathan S. Berg
Other affiliations: Albert Einstein College of Medicine, Baylor College of Medicine
Bio: Jonathan S. Berg is an academic researcher from University of North Carolina at Chapel Hill. The author has contributed to research in topics: Exome sequencing & Genetic testing. The author has an hindex of 51, co-authored 163 publications receiving 21972 citations. Previous affiliations of Jonathan S. Berg include Albert Einstein College of Medicine & Baylor College of Medicine.
Topics: Exome sequencing, Genetic testing, Exome, Medicine, Population
Papers published on a yearly basis
Papers
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Daniel C. Koboldt1, Robert S. Fulton1, Michael D. McLellan1, Heather Schmidt1 +352 more•Institutions (35)
TL;DR: The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.
Abstract: We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.
9,355 citations
Brigham and Women's Hospital1, Partners HealthCare2, University of North Carolina at Chapel Hill3, University of California, Los Angeles4, University of Alabama at Birmingham5, Geisinger Health System6, Baylor College of Medicine7, University of California, San Francisco8, Stanford University9, American College of Medical Genetics10, National Institutes of Health11
TL;DR: It is recommended that laboratories performing clinical sequencing seek and report mutations of the specified classes or types in the genes listed here and encourage the creation of an ongoing process for updating these recommendations at least annually as further data are collected.
2,215 citations
TL;DR: A patient’s family pursues genetic testing that shows a “likely pathogenic” variant for the condition on the basis of a study in an original research publication, and a different variant is found that is determined to be pathogenic.
Abstract: On autopsy, a patient is found to have hypertrophic cardiomyopathy The patient’s family pursues genetic testing that shows a “likely pathogenic” variant for the condition on the basis of a study in an original research publication Given the dominant inheritance of the condition and the risk of sudden cardiac death, other family members are tested for the genetic variant to determine their risk Several family members test negative and are told that they are not at risk for hypertrophic cardiomyopathy and sudden cardiac death, and those who test positive are told that they need to be regularly monitored for cardiomyopathy on echocardiography Five years later, during a routine clinic visit of one of the genotype-positive family members, the cardiologist queries a database for current knowledge on the genetic variant and discovers that the variant is now interpreted as “likely benign” by another laboratory that uses more recently derived population-frequency data A newly available testing panel for additional genes that are implicated in hypertrophic cardiomyopathy is initiated on an affected family member, and a different variant is found that is determined to be pathogenic Family members are retested, and one member who previously tested negative is now found to be positive for this new variant An immediate clinical workup detects evidence of cardiomyopathy, and an intracardiac defibrillator is implanted to reduce the risk of sudden cardiac death
928 citations
TL;DR: Using conditional ablation, it is shown that Dnmt3a loss progressively impairs hematopoietic stem cell differentiation over serial transplantation, while simultaneously expanding HSC numbers in the bone marrow.
Abstract: Margaret Goodell, Wei Li and colleagues report conditional ablation of the Dnmt3a DNA methyltransferase in hematopoietic stem cells (HSCs) in mice. They show that Dnmt3a is critical for epigenetic silencing of HSC regulatory genes and for HSC differentiation.
909 citations
TL;DR: The American College of Medical Genetics and Genomics has developed the following professional standards and guidelines to assist clinical laboratories with the validation ofNext-generation sequencing methods and platforms, the ongoing monitoring of next- generation sequencing testing to ensure quality results, and the interpretation and reporting of variants found using these technologies.
784 citations
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TL;DR: Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends thatclinical molecular genetic testing should be performed in a Clinical Laboratory Improvement Amendments–approved laboratory, with results interpreted by a board-certified clinical molecular geneticist or molecular genetic pathologist or the equivalent.
17,834 citations
TL;DR: A practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics, which makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries.
Abstract: The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.
10,947 citations
TL;DR: This work has revealed the genomic landscapes of common forms of human cancer, which consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of "hills" (Genes altered infrequently).
Abstract: Over the past decade, comprehensive sequencing efforts have revealed the genomic landscapes of common forms of human cancer. For most cancer types, this landscape consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of “hills” (genes altered infrequently). To date, these studies have revealed ~140 genes that, when altered by intragenic mutations, can promote or “drive” tumorigenesis. A typical tumor contains two to eight of these “driver gene” mutations; the remaining mutations are passengers that confer no selective growth advantage. Driver genes can be classified into 12 signaling pathways that regulate three core cellular processes: cell fate, cell survival, and genome maintenance. A better understanding of these pathways is one of the most pressing needs in basic cancer research. Even now, however, our knowledge of cancer genomes is sufficient to guide the development of more effective approaches for reducing cancer morbidity and mortality.
6,441 citations
5,867 citations
TL;DR: This review summarizes the clinical efficacy, perspectives, and future challenges of using PD-1/PD-L1-directed antibodies in the treatment of breast cancer.
Abstract: Immune checkpoint inhibition represents a major recent breakthrough in the treatment of malignant diseases including breast cancer. Blocking the programmed death receptor-1 (PD-1) and its ligand, PD-L1, has shown impressive antitumor activity and may lead to durable long-term disease control, especially in the triple-negative subtypes of breast cancer (TNBC). Although immune checkpoint blockade is generally well tolerated, specific immune-related adverse events (irAEs) may occur. This review summarizes the clinical efficacy, perspectives, and future challenges of using PD-1/PD-L1-directed antibodies in the treatment of breast cancer.
5,777 citations