About

Arupa Ganguly, PhD, is a Professor of Genetics at the Hospital of the University of Pennsylvania and serves as the Director of the Genetic Diagnostic Laboratory in the Department of Genetics at the University of Pennsylvania School of Medicine. Her educational background includes a B.S. and M.S. in Physics from Calcutta University and a Ph.D. in Biophysics from the University of Calcutta. She is also board-certified in Clinical Molecular Genetics by the American Board of Medical Genetics. Her research expertise focuses on the genetic analysis of predisposition to retinoblastoma and uveal melanoma. She investigates the gene expression profiles of retinoblastoma tumors to address clinical questions related to treatment response, metastasis potential, and the molecular basis of tumorigenesis, particularly in relation to retinal progenitor cells. Additionally, her work on uveal melanoma aims to develop gene signatures predictive of metastasis and to understand the molecular mechanisms underlying the development of this rare ocular cancer. Dr. Ganguly provides clinical molecular genetic testing services for hereditary conditions such as colon cancer, Li Fraumeni syndrome, retinoblastoma, and sporadic uveal melanoma, among others. Her laboratory is a reference and training center for testing in the United States, and she collaborates on research projects including the molecular genetics of congenital hyperinsulinism.

Research topics

• Medicine
• Biology
• Genetics
• Virology
• Molecular biology
• Internal medicine
• Oncology
• Bioinformatics
• Cancer research
• Computational biology
• Chemistry

Selected publications

• High‐Resolution Genomic Characterization of <scp>WAGR</scp> Spectrum Disorder: Insights From a Novel Cohort and Literature Synthesis, and Validation of Patient‐Reported Data

  American Journal of Medical Genetics Part A · 2026-04-12

  articleOpen access

  WAGR spectrum disorder (WAGRSD) is an ultra-rare congenital disorder caused by heterozygous deletion of chromosome 11p13. While classically associated with Wilms tumor, Aniridia, Genitourinary anomalies, and a Range of developmental delays, accurate delineation of the deletion is critical for prognosis because the phenotypic spectrum extends well beyond this tetrad. To improve diagnostic resolution, we developed and validated a high-density custom CGH-SNP array for precise breakpoint mapping of 11p13. We present a molecularly confirmed cohort of 23 new patients and integrate these with 91 published cases, forming the largest combined cohort to date (N = 114) with detailed genotype-phenotype information. Key findings include: (1) the custom array provided superior genomic resolution compared to standard clinical arrays; (2) seven patients (6.1%) were found to have a dual diagnosis of WAGRSD and Potocki-Shaffer syndrome (PSS)-a contiguous-gene syndrome characterized by multiple osteochondromas that requires distinct surveillance; (3) in 42 patients with fully defined deletions (n = 42, 38% of the cohort), no statistically significant association was observed between deletion of LMO2 (or other candidate genes) and Wilms tumor risk; and (4) phenotypic frequencies in this medically validated cohort closely aligned with prior caregiver-reported registry data, validating patient-driven registries as a reliable resource for rare disease research. Together, these findings underscore the necessity of high-resolution genomic testing to guide counseling, refine anticipatory management-including screening for PSS-related complications-and expand the phenotypic understanding of 11p13 deletion disorders.

  PublisherDOI

• Noncoding Variants in Intron 2 of <i>HK1</i> Associated With Hyperinsulinism With Variable Clinical Phenotype

  The Journal of Clinical Endocrinology & Metabolism · 2026-03-07

  articleOpen accessSenior author

  INTRODUCTION: Non-coding variants in HK1 were first associated with congenital hyperinsulinism (HI) in a large family with diazoxide-responsive HI in 2008. Since then, additional cases have been reported in the literature with non-coding variants in HK1 associated with variable HI phenotypes. METHODS: We sequenced a 350bp region in intron 2 of HK1 in 281 individuals with genetics negative HI to identify additional cases related to non-coding HK1 variants and to characterize the clinical features of these cases. RESULTS: We identified 16 unique non-coding variants in intron 2 of HK1 in 18 individuals with genetics negative HI (18/281, 6.4%). In seven cases (7/18, 39%), the HK1 variant was inherited from a parent (2 maternal, 5 paternal), two are known to be affected with HI. In nine cases, the HK1 variant was de novo (9/18, 50%). The age of presentation of HI ranged from day of life one to 21 months of age. Seven cases had diazoxide-responsive HI (7/18, 39%). Eleven cases were diazoxide unresponsive (11/18, 61%); five underwent pancreatectomy at ages ranging from six months to three years of age. CONCLUSIONS: Non-coding variants in intron 2 of the HK1 gene have now been associated with HI in a growing number of cases. Our findings suggest that a significant proportion of individuals with negative genetics in genes currently known to be associated with HI may harbor HK1 intron 2 variants. Identifying these cases is important for clinical care as well as for assessing recurrence risk for families.

  PublisherDOI

• Supplemental data from: Determinants of hyperinsulinism severity in children with Beckwith-Wiedemann Syndrome

  Open MIND · 2026-01-08

  dataset

  Context: Congenital hyperinsulinism (HI) is a serious clinical feature of Beckwith-Wiedemann syndrome (BWS) causing severe hypoglycemia. The relationship between BWS genotypes and HI severity is not well understood. Objective: Investigate the relationship between molecular determinants of patients with BWS and HI with measures of HI severity. Design: Retrospective cohort study including 85 children from 2009-2024. Setting: All patients evaluated at single, tertiary care center. Patients: BWS genotype frequency included 41 children with pUPD11, 24 with IC2 LOM, eight with 11p15 chromosomal anomalies, six with GWpUPD, four with IC1 GOM, and two with CDKN1C. Interventions: Retrospectively reviewed interventions included maximum glucose infusion rate (max GIR), diazoxide responsiveness, and surgery. Main Outcome Measures: Primary outcome was association between BWS genotypes and measures of HI severity. Secondary outcomes included the relationship between pUPD11 length and presence of K-ATP variants with diazoxide responsiveness and surgical need. Results: Significant differences presented among genotypes in max GIR (p = 0.004), enteral dextrose requirements (p = 0.029), and pancreatectomy (p = 0.012). Most patients with IC2 LOM, IC1 GOM or CDKN1C were diazoxide responsive and did not require surgery. Patients with pUPD11 were more likely to be diazoxide unresponsive and require surgery, especially if pUPD11 length extended into the K-ATP gene region and if a pathogenic variant in the ABCC8 or KCNJ11 was present. Conclusion: Patients with pUPD11 experience more severe HI, while patients with IC2 LOM, IC1 GOM, and CDKN1C exhibit milder disease. Based on our findings, we designed a genetic testing algorithm to guide clinical management.

  DOI

• P722: Clinical features indicative of positive genetic test outcome in a series of prenatal cases of Beckwith-Wiedemann syndrome

  Genetics in Medicine Open · 2026-01-01

  articleOpen accessSenior author
  PublisherDOI

• Determinants of hyperinsulinism severity in children with Beckwith-Wiedemann syndrome

  The Journal of Clinical Endocrinology & Metabolism · 2026-02-06 · 1 citations

  article

  CONTEXT: Congenital hyperinsulinism (HI) is a serious clinical feature of Beckwith-Wiedemann syndrome (BWS) causing severe hypoglycemia. The relationship between BWS genotypes and HI severity is not well understood. OBJECTIVE: Investigate the relationship between molecular determinants of patients with BWS and HI with measures of HI severity. DESIGN: Retrospective cohort study including 85 children from 2009-2024. SETTING: All patients evaluated at single, tertiary care center. PATIENTS: BWS genotype frequency included 41 children with pUPD11, 24 with IC2 LOM, eight with 11p15 chromosomal anomalies, six with GWpUPD, four with IC1 GOM, and two with CDKN1C. INTERVENTIONS: Retrospectively reviewed interventions included maximum glucose infusion rate (max GIR), diazoxide responsiveness, and surgery. MAIN OUTCOME MEASURES: Primary outcome was association between BWS genotypes and measures of HI severity. Secondary outcomes included the relationship between pUPD11 length and presence of K-ATP variants with diazoxide responsiveness and surgical need. RESULTS: Significant differences presented among genotypes in max GIR (p = 0.004), enteral dextrose requirements (p = 0.029), and pancreatectomy (p = 0.012). Most patients with IC2 LOM, IC1 GOM or CDKN1C were diazoxide responsive and did not require surgery. Patients with pUPD11 were more likely to be diazoxide unresponsive and require surgery, especially if pUPD11 length extended into the K-ATP gene region and if a pathogenic variant in the ABCC8 or KCNJ11 was present. CONCLUSION: Patients with pUPD11 experience more severe HI, while patients with IC2 LOM, IC1 GOM, and CDKN1C exhibit milder disease. Based on our findings, we designed a genetic testing algorithm to guide clinical management.

  PublisherDOI

• Increasing Paternal Age Associated With Elevated Risk of De Novo Mutations in Offspring Diagnosed With Sporadic Bilateral Retinoblastoma

  Pediatric Blood & Cancer · 2025-07-30

  articleOpen access

  BACKGROUND: The impact of paternal exposures on de novo germline mutations leading to bilateral sporadic retinoblastoma in offspring is largely unknown. This malignancy results from mutations of both alleles of the RB1 tumor suppressor gene in a retinal cell. Hence, in this study we aimed to investigate the role of paternal age, gonadal radiation exposure, and smoking on different types of de novo RB1 mutations in a cohort of children with bilateral sporadic retinoblastoma. METHODS: We utilized data from two multi-institutional studies consisted of 172 children diagnosed with sporadic bilateral retinoblastoma who had available information on paternal de novo RB1 mutations. Information on paternal radiation exposure, paternal smoking, and paternal age were obtained from structured questionnaires. Exact logistic regression was utilized to estimate the association between each paternal characteristic and the risk of various types of de novo mutations in offspring. RESULTS: The results revealed a significant association between young paternal age (< 25) and decreased risk of any type of de novo RB1 mutations in offspring compared to children with no mutation detected (adjusted odds ratio [OR] 0.19; 95% confidence interval [CI] 0.04-0.98). In addition, a significant trend toward elevated risk of de novo mutations in offspring with increasing paternal age was detected (adjusted OR 4.01; 95% CI 1.07-15.76). No statistically significant association was identified for the other investigated paternal characteristics. CONCLUSION: Our study suggests a significant role for increasing paternal age in the development of sporadic bilateral retinoblastoma by elevating the risk of de novo RB1 mutations in offspring. These findings shed light on the potential causal mechanisms underlying the development of sporadic retinoblastoma.

  PublisherOA PDFDOI

• Congenital Hyperinsulinism and Long QT Syndrome Attributable to a Variant in KCNE1

  Hormone Research in Paediatrics · 2025-01-08 · 1 citations

  articleOpen access

  INTRODUCTION: This is a report of a child with congenital hyperinsulinism associated with a loss-of-function variant in KCNE1. KCNE1 encodes a human potassium channel accessory (beta) subunit that modulates potassium channel Kv7.1 (encoded by KCNQ1). Loss-of-function pathogenic variants in either the KCNQ1 or KCNE1 genes result in long QT syndrome by causing prolongation in the action potential duration at the cellular level. In addition to long QT syndrome, the phenotype associated with loss-of-function pathogenic variants in KCNQ1 is characterized by postprandial hyperinsulinemic hypoglycemia. CASE PRESENTATION: Clinical data for the proband were extracted from the medical records. The proband presented with fasting hypoglycemia due to hyperinsulinism in early childhood as well as postprandial hypoglycemia triggered by carbohydrates and by protein. Whole-exome sequencing was undertaken in genomic DNA isolated from proband and both parents. Whole-exome sequencing revealed a variant in KCNE1 inherited from the father, who also has a history of hyperinsulinism. Both the patient and father were subsequently diagnosed with long QT syndrome. The proband and father underwent phenotype testing including fasting test, oral glucose tolerance test, oral protein tolerance test, and exercise tolerance test. CONCLUSIONS: This case illustrates that loss-of-function variants in KCNE1, similar to KCNQ1, are associated with a cardiac and a beta cell phenotype, and thus, this patient population should be screened for hypoglycemia, particularly in the postprandial state.

  PublisherOA PDFDOI

• Metastasis-free survival outcomes of uveal melanoma based on The Cancer Genome Atlas classification in 1585 cases

  Canadian Journal of Ophthalmology · 2025-06-19 · 1 citations

  article
  PublisherDOI

• Somatic Genetic Testing Provides Diagnosis of Verrucous Venous Malformation in an Individual with Discrepant Radiology, Pathology, and Clinical Findings

  Journal of Vascular Anomalies · 2025-09-19

  articleOpen access

  Verrucous venous malformation (VVM) is frequently misdiagnosed. This individual demonstrates the value of genetic testing to inform correct diagnosis. Consent was provided for retrospective chart review and publication. At birth, the affected individual had a red flat patch with overgrowth of his right hand, arm, and shoulder. The overgrowth and red color persisted and began to cause pain, which prompted his initial evaluation at age 10 years, leading to a diagnosis of a capillary vascular malformation and overgrowth. Routine magnetic resonance imaging of the right arm showed no definitive vascular anomaly. At 12 years old, hyperkeratosis prompted a biopsy for diagnosis. Pathology from 2 skin biopsies was most consistent with a capillary malformation and showed mildly acanthotic epidermis with hyperkeratosis overlying dilated, thin-walled vascular channels. We performed a 34-gene somatic genetic testing panel on the biopsy tissue. Results showed a likely pathogenic variant in the MAP3K3 gene c.674C&gt;T, p.Ser225Phe at variant allele fraction of 4.2%–4.6% from sample 1 and 7.3%–8.0% from sample 2, confirming the diagnosis of VVM. Somatic genetic testing provided this affected individual with the diagnosis of VVM when radiology, pathology, and clinical findings were discrepant. This new genetic diagnosis influences treatment and prognosis.

  PublisherDOI

• Multiple Genomic Technologies Validate Rare Novel Variant and Direct Medical Care in Vascular Anomalies

  American Journal of Medical Genetics Part A · 2025-07-04

  articleOpen access

  Some vascular anomalies, such as hamartomas associated with PTEN hamartoma tumor syndrome (PHTS) and fibroadipose vascular anomaly (FAVA, often due to PI3KCA variants), share similar clinical, radiological, and histopathological presentations that challenge clinicians to provide an accurate diagnosis. Genetic testing can help clinicians differentiate these two vascular anomalies to provide proper treatment for patients. An 11-year-old female with macrocephaly presented with a painful lesion in her right ankle and was initially diagnosed with FAVA and treated with sirolimus. Initial genetic testing from a biopsy sample was negative. Subsequently, however, repeat clinical genetic testing and research deep exome sequencing from a second tissue biopsy sample identified a mosaic variant in PTEN (NM_00314.7) c.683delA p.Asn228Ilefs*28 with a variant allele fraction (VAF) of 2.0%-2.1%, ultimately changing the diagnosis from FAVA to a PTEN hamartoma. To evaluate the germline status of this patient, PTEN sequencing and deletion duplication testing was sent from saliva and identified a different variant in PTEN (NM_000314.4) c.202_209+18delins27, estimated to be 20%-30% VAF. Sanger sequencing validated this novel variant as germline, leading to cancer screening in the patient. This case exemplifies the need for genetic reevaluation as sequencing technology continues to update rapidly, repeat sampling in cases of suspected mosaicism, the two-hit hypothesis in the development of vascular malformations, and emphasizes the importance of genetic diagnosis in vascular malformations, especially in this case which led to the identification of a cancer predisposition syndrome.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01CA118580

  NIH · $3.5M · 2013

• NIH Grant R21CA123196

  NIH · $352k · 2010

• Mutation Profile as Translatable Prognostic Biomarker of Uveal Melanoma

  NIH · $383k · 2015–2018

• Islet Dysregulation in Infants with Congenital Hyperinsulinism

  NIH · $9.4M · 1999–2025

Frequent coauthors

• Carol L. Shields

  Wills Eye Hospital

  81 shared

• Charles A. Stanley

  Children's Hospital of Philadelphia

  56 shared

• Darwin J. Prockop

  Texas A&M University

  40 shared

• Jerry A. Shields

  Thomas Jefferson University

  36 shared

• Jennifer M. Kalish

  University of Pennsylvania

  29 shared

• N. Scott Adzick

  University of Pennsylvania

  26 shared

• Kim E. Nichols

  St. Jude Children's Research Hospital

  25 shared

• Diva D. De León

  Children's Hospital of Philadelphia

  23 shared

Education

• B.S., Physics

  Calcutta University

  1974

• M.S., Physics

  Calcutta University

  1977

• Ph.D., Biophysics

  University of Calcutta

  1984

• Other, Clinical Molecular Genetics

  American Board of Medical Genetics

  1999

• Other, Clinical Molecular Genetics

  American Board of Medical Genetics

  2009

Awards & honors

• FACMG (Clinical Molecular Genetics) American Board of Medica…
• FACMG (Clinical Molecular Genetics) American Board of Medica…