Edward D Esplin

Edward D Esplin
Stanford Medicine | Stanford · Department of Genetics

M.D., Ph.D., FACMG, FACP

About

141
Publications
16,558
Reads
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2,415
Citations
Introduction
Familial adenomatous polyposis (FAP) is a hereditary colon cancer syndrome caused by the APC gene, which affects children as young as 7 years of age and contributes to overall colon cancer incidence. I am using genome/RNASeq/proteomic techniques to elucidate the molecular cascade of FAP, study the evolution of early colon tumors and identify novel biomarkers and therapeutics relevant to both hereditary and sporadic colon cancer, in an effort to apply principles of genomic medicine.
Additional affiliations
September 2014 - present
Invitae
Position
  • Clinical Geneticist
Description
  • Head of Clinical Studies and Medical Information
July 2013 - present
Stanford Medicine
Position
  • Clinical Scholar
Description
  • Clinical Scholar in the Snyder Lab
July 2011 - June 2013
Stanford Medicine
Position
  • Medical Genetics, residency/fellowship
Description
  • Medical Genetics residency/fellowship clinical training.
Education
July 1995 - June 2005
July 1995 - May 2005
University of Texas Southwestern Medical Center
Field of study
  • Genetics and Development
September 1991 - June 1992
Dixie State University
Field of study
  • Pre-Business, Pre-Medicine (Associate of Arts)

Publications

Publications (141)
Article
Full-text available
The PPP2R1B gene, which encodes the β isoform of the A subunit of the serine/threonine protein phosphatase 2A (PP2A), was identified as a putative human tumor suppressor gene. Sequencing of thePPP2R1B gene, located on human chromosome 11q22-24, revealed somatic alterations in 15% (5 out of 33) of primary lung tumors, 6% (4 out of 70) of lung tumor–...
Article
Full-text available
Comparative genomic hybridization (CGH) arrays have significantly changed the approach to identifying genetic alterations causing intellectual disability and congenital anomalies. Several studies have described the microduplication of Xp22.31, involving the STS gene. In such reports characteristic features and pathogenicity of Xp22.31 duplications...
Article
Full-text available
Importance: Hereditary factors play a key role in the risk of developing several cancers. Identification of a germline predisposition can have important implications for treatment decisions, risk-reducing interventions, cancer screening, and germline testing. Objective: To examine the prevalence of pathogenic germline variants (PGVs) in patients...
Article
Full-text available
IMPORTANCE Both germline genetic testing and tumor DNA sequencing are increasingly used in cancer care. The indications for testing and utility of these 2 tests differ, and guidelines recommend that germline analysis follow tumor sequencing in certain patients to determine whether particular variants are of somatic or germline origin. Broad clinica...
Article
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Purpose: An estimated 10% of breast and ovarian cancers result from hereditary causes. Current testing guidelines for germ line susceptibility genes in patients with breast carcinoma were developed to identify carriers of BRCA1/ 2 variants and have evolved in the panel-testing era. We evaluated the capability of the National Comprehensive Cancer N...
Article
Full-text available
To chart cell composition and cell state changes that occur during the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC), we generated single-cell chromatin accessibility profiles and single-cell transcriptomes from 1,000 to 10,000 cells per sample for 48 polyps, 27 normal tissues and 6 CRCs collected from patients...
Article
Full-text available
Objective Hereditary uterine cancer (UC) is traditionally associated with pathogenic/likely pathogenic germline variants (PGVs) in Lynch syndrome genes or PTEN; however, growing evidence supports a role for other genes that may reveal new clinical management options. In this study we assessed the prevalence and potential clinical impact of PGVs ide...
Article
e17593 Background: Ovarian cancer is one of the most common gynecological malignancies. Because of the absence of effective screening methods, ovarian cancer is usually diagnosed at late stages contributing to high mortality rates. Patients with BRCA1 and BRCA2 pathogenic germline variants (PGVs) harbor elevated risk of developing both ovarian and...
Article
10589 Background: Germline and somatic genetic testing are established tools for the management of cancer patients. Somatic testing is primarily used to inform therapy and germline testing is used to diagnose hereditary cancer predisposition syndromes. While somatic testing can detect germline variants, the interpretation and reporting algorithms a...
Article
10504 Background: Germline genetic testing for patients (pts) with colorectal cancer (CRC) is currently recommended for those diagnosed prior to age 50, as well as other select cases based on personal and/or family history criteria. Whether universal germline multi-gene panel testing (MGPT) should be performed in all pts with CRC remains uncertain...
Article
10523 Background: Melanoma has recently been suggested to be a highly heritable cancer with high twin-twin concordance. In contrast, prior studies on patients with familial atypical multiple mole melanoma (FAMMM) syndrome, multiple primary melanomas and early age of onset, all known to be associated with germline CDKN2A/CDK4 pathogenic variants, su...
Article
10500 Background: Approximately 10-15% of prostate cancer (PCa) patients (pts) have a pathogenic germline variant (PGV). Identification of a PGV has important implications affecting decisions regarding cancer screening, treatment selection, and family cascade testing. There exists limited data documenting real world recommendations post germline ge...
Article
10588 Background: Detection of pathogenic germline variants (PGVs) has implications for cancer screening, prognostication, treatment selection, clinical trial enrollment and family testing. Published guidelines provide indications for PGV testing, determined by clinical and demographic factors, but these leave a significant number of cases missed b...
Article
4569 Background: Prior studies of the UC germline landscape centered around White patients with minimal representation of other racial populations. Herein, we examine the frequency of germline pathogenic and likely pathogenic (P/LP) variants in 2,582 patients with UC from various racial populations. Methods: 2,582 patients with UC underwent germlin...
Article
Full-text available
Although multiple factors can influence the uptake of cascade genetic testing, the impact of proband indication has not been studied. We performed a retrospective, cross-sectional study comparing cascade genetic testing rates among relatives of probands who received either diagnostic germline testing or non-indication-based proactive screening via...
Preprint
Aberrant shifts in DNA methylation have long been regarded as an early marker for cancer onset and progression. To chart DNA methylation changes that occur during the transformation from normal healthy colon tissue to malignant colorectal cancer (CRC), we collected over 50 samples from 15 familial adenomatous polyposis (FAP) and non-FAP colorectal...
Article
Full-text available
Consensus guidelines for hereditary breast and ovarian cancer include management recommendations for pathogenic/likely pathogenic (P/LP) variants in ATM, CHEK2, PALB2, and other DNA damage repair (DDR) genes beyond BRCA1 or BRCA2. We report on clinical management decisions across three academic medical centers resulting from P/LP findings in DDR ge...
Article
As the costs for next-generation sequencing technology have decreased and our understanding of the clinical utility of genetic testing has increased, there has been a concomitant increase in questions regarding when and how genetic test results should be used for the medical management of patients. The American College of Medical Genetics and Genom...
Article
Full-text available
Hypertrophic cardiomyopathy (HCM) has historically been diagnosed phenotypically. Through genetic testing, identification of a molecular diagnosis (MolDx) is increasingly common but the impact on pediatric patients is unknown. This was a retrospective study of next-generation sequencing data for 602 pediatric patients with a clinician-reported hist...
Article
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The imminent release of tissue atlases combining multichannel microscopy with single-cell sequencing and other omics data from normal and diseased specimens creates an urgent need for data and metadata standards to guide data deposition, curation and release. We describe a Minimum Information about Highly Multiplexed Tissue Imaging (MITI) standard...
Article
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Background Little is known about the true rate of pathogenic (P)/likely pathogenic (LP) germline alterations in Hispanic men with prostate cancer as most studies analyzing the prevalence of P/LP germline alterations were performed in a largely non-Hispanic white population (NHW). Methods We performed a retrospective analysis of two separate cohort...
Article
Clinical guidelines recommend universal tumor screening (UTS) of colorectal and endometrial cancers for Lynch syndrome (LS). There are limited guidelines for how to integrate germline testing and somatic tumor testing after a mismatch repair deficient (dMMR) tumor is identified. We sought to characterize current practice patterns and barriers to pr...
Article
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Background and Aims To determine prevalence and clinical utility of pathogenic germline variants (PGV) in gastric and esophageal cancer patients using universal genetic testing approach. Methods We undertook a prospective study of germline sequencing using an > 80 gene next-generation sequencing platform among patients with gastric and esophageal...
Article
Background Germline studies in testicular cancer have focused on unselected populations but so far have not led to recommendations for testicular cancer screening. Objective Herein, we hypothesized that men with testicular cancer and an additional risk factor for hereditary cancer predisposition carry a higher rate of pathogenic variants than men...
Article
Full-text available
Background and aims CDH1 germline variants have been linked to heritability in diffuse gastric (DGC) and lobular breast cancer (LBC). Studies have not yet assessed whether CDH1 is a cancer-susceptibility gene in other cancers. Herein, we mapped the landscape of pathogenic and likely pathogenic (P/LP) germline variants in CDH1 across various cancers...
Chapter
Lung cancer is the most prevalent cancer worldwide. About 80% to 85% of lung cancers are non-small cell lung cancer (NSCLC). One of the major types of NSCLC is lung adenocarcinoma (LUAD), which solely accounts for approximately 40% of all cases. Although there has been a dramatic therapeutic improvement, the prognostic trajectory has relied on prim...
Preprint
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The colon is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota, and affects overall health. To better understand its organization, functions, and its regulation at a single cell level, we performed CODEX multiplexed imaging, as well as single...
Article
Introduction: Professional guidelines support genetic testing (GT) for dilated, hypertrophic, restrictive, arrhythmogenic, and peripartum cardiomyopathy to confirm a diagnosis, guide management, enable clinical trials, and/or allow more informed genetic counseling. Analysis of de-identified data from a commercial laboratory showed that 1 in 4 indiv...
Article
Full-text available
Data from germline testing in unselected patients with hepatobiliary cancers are limited. Identification of germline predisposition can have important implications on cancer treatment and family counseling. To determine prevalence of pathogenic germline variants (PGV) in hepatobiliary cancer patients we undertook a prospective multi-site study of g...
Preprint
The Human BioMolecular Atlas Program aims to compile a reference atlas for the healthy human adult body at the cellular level. Functional tissue units (FTU, e.g., renal glomeruli and colonic crypts) are of pathobiological significance and relevant for modeling and understanding disease progression. Yet, annotation of FTUs is time consuming and expe...
Article
Background: Germline variants in fumarate hydratase (FH) are associated with autosomal dominant (AD) hereditary leiomyomatosis and renal cell cancer (HLRCC) and autosomal recessive (AR) fumarase deficiency (FMRD). The prevalence and cancer penetrance across different FH variants remain unclear. Methods: A database containing 120,061 records from...
Article
Full-text available
INTRODUCTION: To report the prevalence and outcomes of unselected pancreatic cancer (PC) patients with pathogenic/likely pathogenic germline variants (PGVs) detected using a universal testing approach. METHODS: We undertook a prospective, multisite study of germline sequencing using a >80 gene next-generation sequencing platform among 250 patien...
Article
A missense variant (p.Ser428Phe [S428F]) in the CHEK2 gene is reportedly associated with a 2–3 fold increase in breast cancer risk in Ashkenazi Jews. This study aimed to re-evaluate cancer risks conferred by the CHEK2 S428F variant in Ashkenazi Jews. De-identified data from CHEK2 S428F variant carriers sequenced with multigene panels were analyzed....
Article
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Background The use of proactive genetic screening for disease prevention and early detection is not yet widespread. Professional practice guidelines from the American College of Medical Genetics and Genomics (ACMG) have encouraged reporting pathogenic variants that confer personal risk for actionable monogenic hereditary disorders, but only as seco...
Article
Full-text available
PURPOSE Strict clinical criteria used by Medicare for germline testing for Lynch syndrome (LS) could lead to missed diagnoses of hereditary cancer syndromes given variable individual and family phenotypes. The aim of this study was to compare rates and spectrum of pathogenic or likely pathogenic (P/LP) variants in LS and other hereditary cancer gen...
Article
Full-text available
Ovarian cancer (OVCA) patients may carry genes conferring cancer risk to biological family; however, fewer than one-quarter of patients receive genetic testing. “Traceback” cascade testing —outreach to potential probands and relatives—is a possible solution. This paper outlines a funded study (U01 CA240747-01A1) seeking to determine a Traceback pro...
Poster
4118 Background: Germline variations in cancer susceptibility genes have important implications on treatment and family counseling in pancreatic cancer (PC). We report the prevalence and clinical outcomes of unselected PC patients with pathogenic germline variants (PGV) detected using a universal testing approach. Methods: We undertook a prospectiv...
Article
Full-text available
Importance Familial hypercholesterolemia (FH) is the most common inherited cardiovascular disease and carries significant morbidity and mortality risks. Genetic testing can identify affected individuals, but some array-based assays screen only a small subset of known pathogenic variants. Objective To identify the number of clinically significant v...
Article
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In Reply Dr Sorscher’s comments appropriately note that classification of pathogenic germline variants (PGVs) as high or moderate penetrance is based primarily on studies in individuals of families with a known family history of increased cancer risk. In the Interrogating Cancer Etiology Using Proactive Genetic Testing (INTERCEPT) study,¹ individua...
Article
10534 Background: With the growing indications for germline testing in prostate cancer (PCa), there is accumulating evidence that African American and Hispanic men with PCa are significantly under-tested compared to non-Hispanic white (NHW) men. Given this, little is known about the pathogenic germline variant landscape in Hispanic men with PCa. Me...
Article
10515 Background: With the advent of DTC genetic testing, individuals have access to genetic testing without input from a healthcare professional. DTC testing now exists for the 3 Ashkenazi Jewish (AJ) BRCA1/2 founder variants. DTC testing may provide false reassurance to individuals that they do not carry a pathogenic or likely pathogenic variant...
Article
10514 Background: Colorectal cancer (CRC) affects approximately 104,000 patients (pts) annually in the United States, up to 45% of which are estimated to be genetic and/or familial. Aligned with clinical guidelines, in 2020, a large U.S. insurer established Medical Policy allowing for and reimbursing germline genetic testing (GGT) for all CRC pts....
Article
10504 Background: Pathogenic/likely pathogenic (P/LP) germline genetic variants are estimated to occur in 10-15% of all prostate cancer (PCa) patients. However, genetic testing for PCa patients is underutilized, partially due to complicated and restrictive testing guidelines developed at a time when the cost of testing was high. We conducted a stud...
Preprint
Full-text available
Familial adenomatous polyposis (FAP) is a genetic disease causing hundreds of premalignant polyps in affected patients, leading to colorectal cancer (CRC), and is an ideal model to study early transition to CRC. We performed deep multi-omic profiling of 135 normal mucosal, benign and dysplastic polyps and adenocarcinoma samples from 6 FAP patients...
Article
Full-text available
PURPOSE An inherited basis for presumed sporadic neuroendocrine tumor (NET) has been suggested by evidence of familial clustering of NET and a higher incidence of second malignancies in patients and families with NET. To further investigate a potential heritable basis for sporadic neuroendocrine tumors, we performed multigene platform germline anal...
Article
PURPOSE Hepatocellular carcinoma (HCC) has well-defined environmental risk factors. In addition, epidemiologic studies have suggested hereditary risk factors. The goals of this study were to determine the rate of pathogenic and likely pathogenic (P/LP) germline variants in cancer predisposition genes in patients with HCC, possible enrichment of P/L...
Article
Full-text available
Background & Aim Hereditary factors play a role in the development of colorectal cancer (CRC). Identification of germline predisposition can have implications on treatment and cancer prevention. To determine prevalence of pathogenic germline variants (PGV) in CRC patients using an universal testing approach, association with clinical outcomes and t...
Preprint
To chart cell composition and cell state changes that occur during the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC), we generated 451,886 single-cell chromatin accessibility profiles and 208,557 single-cell transcriptomes from 48 polyps, 27 normal tissues, and 6 CRCs collected from patients with and without ge...
Article
Full-text available
Prior studies of the renal cell carcinoma (RCC) germline landscape investigated predominantly patients of European ancestry. We examine the frequency of germline pathogenic and likely pathogenic (P/LP) variants in 1,829 patients with RCC from various ancestries. Overall, P/LP variants are found in 17% of patients, among whom 10.3% harbor one or mor...
Conference Paper
Background: Hereditary factors lay a key role in the risk of develoing breast cancers. Identification of a germline redisosition can have imortant imlications for treatment decisions, risk-reducing interventions, cancer screening, and testing for family members. Aim: To determine the revalence of athogenic or likely athogenic germline mutations (P/...
Conference Paper
Background:Therapeutic and risk management options have expanded for patients harboring pathogenic variants (PVs) in cancer predisposition genes. Historically, testing costs and clinical implementation challenges led to restrictive testing guidelines in many countries. Increasing evidence demonstrates that narrow criteria will miss patients with po...
Conference Paper
Background: Growing evidence indicates that restrictive criteria for determining eligibility of breast cancer patients for germline genetic testing (e.g. NCCN, etc.) can missa significant number who may benefit from testing. However, the clinical utility and outcomes of patients with germline pathogenic variants (“positive patients”) who fall outsi...
Article
Full-text available
Background - Familial hypercholesterolemia (FH) is the most common cardiovascular genetic disorder and, if left untreated, is associated with increased risk of premature atherosclerotic cardiovascular disease, the leading cause of preventable death in the United States. Although FH is common, fatal, and treatable, it is underdiagnosed and undertrea...
Article
Genetic testing can provide definitive molecular diagnoses and guide clinical management decisions from preconception through adulthood. Innovative solutions for scaling clinical genomics services are necessary if they are to transition from a niche specialty to a routine part of patient care. The expertise of specialists, like genetic counselors a...
Article
Introduction: Professional societies recommend genetic testing to improve diagnosis and inform management of inherited cardiovascular disease, yet genetic testing is not widely utilized in cardiovascular practice. To reduce barriers to genetic testing and facilitate following of existing guidelines, we initiated a program of sponsored genetic testi...
Article
e16783 Background: PARP inhibitor (PARPi) treatment was recently approved for pancreatic cancer (PaCa) patients with germline mutations in 2 DNA damage repair (DDR) genes. Despite criteria recommending germline multigene panel testing for all PaCa patients, barriers to testing remain, including among underserved populations, which limit access to p...