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Arupa Ganguly, PhD
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Professor of Genetics at the Hospital of the University of Pennsylvania
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Director, Genetic Diagnostic Laboratory, University of Pennsylvania
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Department: Genetics
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Graduate Group Affiliations
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- Bioengineering e
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Contact information
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415 Anatomy Chemistry Building
35 3620 Hamilton Walk
Philadelphia, PA 19104
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35 3620 Hamilton Walk
Philadelphia, PA 19104
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Office: 215-898-3122
32 Fax: 215-573-5940
32 Lab: 215-573-3020
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32 Fax: 215-573-5940
32 Lab: 215-573-3020
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Email:
GANGULY@MAIL.MED.UPENN.EDU
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GANGULY@MAIL.MED.UPENN.EDU
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Publications
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Links
b8 Search PubMed for articles
ae Genetic Diagnostic Laboratory, Department of Genetics, University of Pennsylvania, School of Medicine
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b8 Search PubMed for articles
ae Genetic Diagnostic Laboratory, Department of Genetics, University of Pennsylvania, School of Medicine
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Education:
21 a B.S. 14 (Physics) c
2c Calcutta University, 1974.
21 9 M.S. 14 (Physics) c
2c Calcutta University, 1977.
21 a Ph.D. 17 (Biophysics) c
2f University of Calcutta, 1984.
21 a FACMG 28 (Clinical Molecular Genetics) c
3b American Board of Medical Genetics, 1999.
21 a FACMG 28 (Clinical Molecular Genetics) c
3b American Board of Medical Genetics, 2009.
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Permanent link21 a B.S. 14 (Physics) c
2c Calcutta University, 1974.
21 9 M.S. 14 (Physics) c
2c Calcutta University, 1977.
21 a Ph.D. 17 (Biophysics) c
2f University of Calcutta, 1984.
21 a FACMG 28 (Clinical Molecular Genetics) c
3b American Board of Medical Genetics, 1999.
21 a FACMG 28 (Clinical Molecular Genetics) c
3b American Board of Medical Genetics, 2009.
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86 Retinoblastoma is a childhood onset ocular cancer caused by mutations in tumor suppressor gene, RB1, present on chromosome 13.
14a RB1 was the first tumor suppressor gene identified and validated the two hit hypothesis of cancer proposed by Alfred Knudson. The burden of lost eye sight in early childhood is very high with this disease – it has been reduced remarkably in the developed countries, but still is a major concern in developing countries.
8b Thus there is a need to reduce the burden of blindness by developing treatment modality that will spare the infant eye and vision.
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1ac An interesting aspect of RB1 is that this gene is inactivated in half of all known cancer. Yet an individual born with a germline mutation in RB1 gene is predisposed to childhood onset eye tumor and a second cancer that can be osteosarcoma if exposed to radiation or melanoma. This means that the RB1 gene product has a very specific role in the development of the retina – a role that is not shared by other tissues.
234 However the cell of origin of retinoblastoma is not known. Therefore by studying the gene expression profile of enucleated retinoblastoma tumors we are attempting to answer a few clinical questions like the clinical response to different treatment options, potential for metastasis and molecular basis of other predictive clinical features. In addition we are trying to identify the expression profiles of genes characteristic of the progenitor cells for retina and define at which stage of retinal cell development does the process of tumorigenesis begin.
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3ee Another recent direction of research is in defining the molecular basis of uveal melanoma. Uveal melanoma is a rare form of ocular cancer in the Western world and the incidence rate is 1 in 100, 000. A significant observation is that almost half of all identified cases of uveal melanoma develop liver metastasis and die within a very short period after the initial diagnosis. Thus it is a major health care issue. The only prognostic features available at this time are monosomy for chromosome 3 along with alterations on chromosomes 1, 6 and 8 and are associated with bad prognosis. These features suggest an underlying genetic predisposition towards melanomas. Uveal melanoma can be mistaken for congenital nevi and may be undiagnosed or under diagnosed. The goals of this project are: i) To develop a gene signature that will be predictors of metastasis based on investigations on fine needle aspirates. ii) To understand the molecular mechanisms regulating the development of uveal melanomas.
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6f This laboratory is also an ABMG accredited laboratory for training clinical molecular genetics fellows.
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121 In addition, I am involved in a collaboration with Dr, Charles Stanley, Children's Hospital of Philadelphia, to undertsand the molecular genetics of congenital hyperinsulinism (CHI). We have recently identified a novel genomic region linked to autosomal dominant inheritance of CHI.
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Description of Research Expertise
58 Genetic Analysis of Predisposition to Retinoblastoma and Uveal Melanoma8
86 Retinoblastoma is a childhood onset ocular cancer caused by mutations in tumor suppressor gene, RB1, present on chromosome 13.
14a RB1 was the first tumor suppressor gene identified and validated the two hit hypothesis of cancer proposed by Alfred Knudson. The burden of lost eye sight in early childhood is very high with this disease – it has been reduced remarkably in the developed countries, but still is a major concern in developing countries.
8b Thus there is a need to reduce the burden of blindness by developing treatment modality that will spare the infant eye and vision.
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1ac An interesting aspect of RB1 is that this gene is inactivated in half of all known cancer. Yet an individual born with a germline mutation in RB1 gene is predisposed to childhood onset eye tumor and a second cancer that can be osteosarcoma if exposed to radiation or melanoma. This means that the RB1 gene product has a very specific role in the development of the retina – a role that is not shared by other tissues.
234 However the cell of origin of retinoblastoma is not known. Therefore by studying the gene expression profile of enucleated retinoblastoma tumors we are attempting to answer a few clinical questions like the clinical response to different treatment options, potential for metastasis and molecular basis of other predictive clinical features. In addition we are trying to identify the expression profiles of genes characteristic of the progenitor cells for retina and define at which stage of retinal cell development does the process of tumorigenesis begin.
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3ee Another recent direction of research is in defining the molecular basis of uveal melanoma. Uveal melanoma is a rare form of ocular cancer in the Western world and the incidence rate is 1 in 100, 000. A significant observation is that almost half of all identified cases of uveal melanoma develop liver metastasis and die within a very short period after the initial diagnosis. Thus it is a major health care issue. The only prognostic features available at this time are monosomy for chromosome 3 along with alterations on chromosomes 1, 6 and 8 and are associated with bad prognosis. These features suggest an underlying genetic predisposition towards melanomas. Uveal melanoma can be mistaken for congenital nevi and may be undiagnosed or under diagnosed. The goals of this project are: i) To develop a gene signature that will be predictors of metastasis based on investigations on fine needle aspirates. ii) To understand the molecular mechanisms regulating the development of uveal melanomas.
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Description of Clinical Expertise
1cf As the Director of the Genetic Diagnostic laboratory, Department of Genetics, I provide clinical molecular genetic testing services for hereditary forms of colon cancer, Li Fraumeni syndrome,Retinoblastoma(RB) and molecular profiling of sporadic uveal mealnoma, Hemophilia A, and Herediatry Hemorrhagic Telangiectasia (HHT or Osler Weber Rendu Syndrome). This laboratory is a reference laboratory for testing RB, HHT and Hemophilia A in the US.6f This laboratory is also an ABMG accredited laboratory for training clinical molecular genetics fellows.
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121 In addition, I am involved in a collaboration with Dr, Charles Stanley, Children's Hospital of Philadelphia, to undertsand the molecular genetics of congenital hyperinsulinism (CHI). We have recently identified a novel genomic region linked to autosomal dominant inheritance of CHI.
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15a Torales LDG, Woodis K, Britt A, Surrey LF, Srinivasan A, Ganguly A, Limmina M, Li D, MacFarland SP, Adams DM, Sheppard SE. : Multiple Genomic Technologies Validate Rare Novel Variant and Direct Medical Care in Vascular Anomalies. Am J Med Genet A. Page: e64126, Jul 2025.
152 Mies G, Tsao NL, Houy A, Coupland SE, Kalirai H, Försti A, Hemminki K, Thomsen H, Stern MH, Shields CL, Damrauer SM, Ewens KG, Ganguly A, Mathieson I. : Meta-analysis of uveal melanoma genome-wide association studies identifies novel risk loci and population effect size heterogeneity. 3a HGG Adv. 6(3): 100465, Jul 2025.
e8 Boodhansingh KE, Lord K, Adzick NS, Bhatti T, Ganguly A, Stanley CA, De Leon DD. : Low-Level Mosaic GCK Mutations in Children With Diazoxide-Unresponsive Congenital Hyperinsulinism. 4f J Clin Endocrinol Metab. 110(7): 1923-1928, Jun 2025.
127 Sigal W, Boodhansingh KE, Ganguly A, Mitteer LM, Stanley CA, De León DD: Congenital Hyperinsulinism and Long QT Syndrome Attributable to a Variant in KCNE1. Horm Res Pediatr 8: 1-10, Jan 2025 Notes: Online ahead of print.
f1 Guzman H, Mitteer LM, Chen P, Juliana CA, Boodhansingh K, Lord K, Ganguly A, De Leon DD. : Functional characterization of a missense variant in INSR associated with hypoketotic hypoglycemia. 3e Front Pediatr. 12: 1493280, Oct 2024.
10a Bansal R, Sener H, Ganguly A, Shields JA, Shields CL: Metastasis-free survival of uveal melanoma by tumor size category based on The Cancer Genome Atlas (TCGA) classification in 1001 cases. Clin Exp Ophthalmol. 43 (eds.). Oct 2024 Notes: Online ahead of print.
12f George AM, Viswanathan A, Best LG, Monahan C, Limmina M, Ganguly A, Kalish JM.: Expanded phenotype and cancer risk in patients with Beckwith-Wiedemann spectrum caused by CDKN1C variants. Am J Med Genet A 194(10): e63777, Oct 2024.
13c Boodhansingh KE, Lord K, Adzick NS, Bhatti T, Ganguly A, Stanley CA, De Leon DD.: Low-level mosaic GCK mutations in children with diazoxide-unresponsive congenital hyperinsulinism. J Clin Endocrinol Metab Oct 2024 Notes: Online ahead of print.
141 Lalonde E, Li D, Ewens K, Shields CL, Ganguly A.: Genome-Wide Methylation Patterns in Primary Uveal Melanoma: Development of MethylSig-UM, an Epigenomic Prognostic Signature to Improve Patient Stratification. Cancers (Basel) 16(15): 2650, Jul 2024.
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Selected Publications
173 Adel Fahmideh M, Ganguly AA, Chambers TM, Bunin GR, Lupo PJ.: Increasing Paternal Age Associated With Elevated Risk of De Novo Mutations in Offspring Diagnosed With Sporadic Bilateral Retinoblastoma. Pediatr Blood Cancer. 72(10): e31936, Oct 2025 Notes: doi: 10.1002/pbc.31936. Epub 2025 Jul 30.15a Torales LDG, Woodis K, Britt A, Surrey LF, Srinivasan A, Ganguly A, Limmina M, Li D, MacFarland SP, Adams DM, Sheppard SE. : Multiple Genomic Technologies Validate Rare Novel Variant and Direct Medical Care in Vascular Anomalies. Am J Med Genet A. Page: e64126, Jul 2025.
152 Mies G, Tsao NL, Houy A, Coupland SE, Kalirai H, Försti A, Hemminki K, Thomsen H, Stern MH, Shields CL, Damrauer SM, Ewens KG, Ganguly A, Mathieson I. : Meta-analysis of uveal melanoma genome-wide association studies identifies novel risk loci and population effect size heterogeneity. 3a HGG Adv. 6(3): 100465, Jul 2025.
e8 Boodhansingh KE, Lord K, Adzick NS, Bhatti T, Ganguly A, Stanley CA, De Leon DD. : Low-Level Mosaic GCK Mutations in Children With Diazoxide-Unresponsive Congenital Hyperinsulinism. 4f J Clin Endocrinol Metab. 110(7): 1923-1928, Jun 2025.
127 Sigal W, Boodhansingh KE, Ganguly A, Mitteer LM, Stanley CA, De León DD: Congenital Hyperinsulinism and Long QT Syndrome Attributable to a Variant in KCNE1. Horm Res Pediatr 8: 1-10, Jan 2025 Notes: Online ahead of print.
f1 Guzman H, Mitteer LM, Chen P, Juliana CA, Boodhansingh K, Lord K, Ganguly A, De Leon DD. : Functional characterization of a missense variant in INSR associated with hypoketotic hypoglycemia. 3e Front Pediatr. 12: 1493280, Oct 2024.
10a Bansal R, Sener H, Ganguly A, Shields JA, Shields CL: Metastasis-free survival of uveal melanoma by tumor size category based on The Cancer Genome Atlas (TCGA) classification in 1001 cases. Clin Exp Ophthalmol. 43 (eds.). Oct 2024 Notes: Online ahead of print.
12f George AM, Viswanathan A, Best LG, Monahan C, Limmina M, Ganguly A, Kalish JM.: Expanded phenotype and cancer risk in patients with Beckwith-Wiedemann spectrum caused by CDKN1C variants. Am J Med Genet A 194(10): e63777, Oct 2024.
13c Boodhansingh KE, Lord K, Adzick NS, Bhatti T, Ganguly A, Stanley CA, De Leon DD.: Low-level mosaic GCK mutations in children with diazoxide-unresponsive congenital hyperinsulinism. J Clin Endocrinol Metab Oct 2024 Notes: Online ahead of print.
141 Lalonde E, Li D, Ewens K, Shields CL, Ganguly A.: Genome-Wide Methylation Patterns in Primary Uveal Melanoma: Development of MethylSig-UM, an Epigenomic Prognostic Signature to Improve Patient Stratification. Cancers (Basel) 16(15): 2650, Jul 2024.
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