Arupa Ganguly, PhD

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Professor of Genetics at the Hospital of the University of Pennsylvania
Director, Genetic Diagnostic Laboratory, University of Pennsylvania
Department: Genetics
Graduate Group Affiliations

Contact information
415 Anatomy Chemistry Building
3620 Hamilton Walk
Philadelphia, PA 19104
Office: 215-898-3122
Fax: 215-573-5940
Lab: 215-573-3020
B.S. (Physics)
Calcutta University, 1974.
M.S. (Physics)
Calcutta University, 1977.
Ph.D. (Biophysics)
University of Calcutta, 1984.
FACMG (Clinical Molecular Genetics)
American Board of Medical Genetics, 1999.
FACMG (Clinical Molecular Genetics)
American Board of Medical Genetics, 2009.
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Description of Research Expertise

Genetic Analysis of Predisposition to Retinoblastoma and Uveal Melanoma

Retinoblastoma is a childhood onset ocular cancer caused by mutations in tumor suppressor gene, RB1, present on chromosome 13.
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.
Thus there is a need to reduce the burden of blindness by developing treatment modality that will spare the infant eye and vision.

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.
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.

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.

Description of Clinical Expertise

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.
This laboratory is also an ABMG accredited laboratory for training clinical molecular genetics fellows.

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.

Selected Publications

Nriagu BN, Williams LS, Brewer N, Surrey LF, Srinivasan AS, Li D, Britt A, Treat J, Crowley TB, O'Connor N, Ganguly A, Low D, Queenan M, Drivas TG, Zackai EH, Adams DM, Hakonarson H, Snyder KM, Sheppard SE.: Microcystic lymphatic malformations in Turner syndrome are due to somatic mosaicism of PIK3CA. Am J Med Genet A Sep 2023.

Sheppard SE, March ME, Seiler C, Matsuoka LS, Kim SE, Kao C, Rubin AI, Battig MR, Khalek N, Schindewolf E, O'Connor N, Pinto E, Priestley JR, Sanders VR, Niazi R, Ganguly A, Hou C, Slater D, Frieden IJ, Huynh T, Shieh JT, Krantz ID, Guerrero JC, Surrey LF, Biko DM, Laje P, Castelo-Soccio L, Nakano TA, Snyder K, Smith CL, Li D, Dori Y, Hakonarson H.: Lymphatic disorders caused by mosaic, activating KRAS variants respond to MEK inhibition. JCI Insight 8: e155888, May 2023.

Jung EM, Bunin GR, Ganguly A, Johnson RA, Spector LG.: The association between maternal nutrient intake during pregnancy and the risk of sporadic unilateral retinoblastoma among offspring. Cancer Epidemiol 2023.

Gill VT, Sabazade S, Herrspiegel C, Ewens KG, Opalko A, Dan N, Christersdottir T, Berg Rendahl A, Shields CL, Seregard S, Ganguly A, Stålhammar G.: A prognostic classification system for uveal melanoma based on a combination of patient age and sex, the American Joint Committee on Cancer and the Cancer Genome Atlas models. Acta Ophthalmol 2023.

Best LG, Duffy KA, George AM, Ganguly A, Kalish JM.: Familial Beckwith-Wiedemann syndrome in a multigenerational family: Forty years of careful phenotyping. Am J Med Genet A 2023.

Boodhansingh KE, Yang Z, Li C, Chen P, Lord K, Becker SA, States LJ, Adzick NS, Bhatti T, Shyng SL, Ganguly A, Stanley CA, De Leon DD.: Localized islet nuclear enlargement hyperinsulinism (LINE-HI) due to ABCC8 and GCK mosaic mutations. Eur J Endocrinol 187: 301-313, Jun 2022.

Lalonde E, Ewens K, Richards-Yutz J, Ebrahimzedeh J, Terai M, Gonsalves CF, Sato T, Shields CL, Ganguly A.: Improved Uveal Melanoma Copy Number Subtypes Including an Ultra-High-Risk Group. Ophthalmol Sci 2: 100121, Jan 2022.

Boodhansingh KE, Rosenfeld E, Lord K, Adzick NS, Bhatti T, Ganguly A, De Leon DD, Stanley CA.: Mosaic GLUD1 Mutations Associated with Hyperinsulinism Hyperammonemia Syndrome. Horm Res Paediatr 2022.

Marques AD, Sherrill-Mix S, Everett JK, Reddy S, Hokama P, Roche AM, Hwang Y, Glascock A, Whiteside SA, Graham-Wooten J, Khatib LA, Fitzgerald AS, Moustafa AM, Bianco C, Rajagopal S, Helton J, Deming R, Denu L, Ahmed A, Kitt E, Coffin SE, Newbern C, Mell JC, Planet PJ, Badjatia N, Richards B, Wang ZX, Cannuscio CC, Strelau KM, Jaskowiak-Barr A, Cressman L, Loughrey S, Ganguly A, Feldman MD, Collman RG, Rodino KG, Kelly BJ, Bushman FD.: SARS-CoV-2 Variants Associated with Vaccine Breakthrough in the Delaware Valley through Summer 2021. mBio 13: e0378821, Feb 2021.

Mazloumi Mehdi, Vichitvejpaisal Pornpattana, Dalvin Lauren A, Yaghy Antonio, Ewens Kathryn G, Ganguly Arupa, Shields Carol L: Accuracy of The Cancer Genome Atlas Classification vs American Joint Committee on Cancer Classification for Prediction of Metastasis in Patients With Uveal Melanoma. JAMA ophthalmology Page: Epub, Jan 2020.

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Last updated: 11/22/2023
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