Arupa Ganguly

faculty photo
Professor of Genetics at the Hospital of the University of Pennsylvania
Director, R&D Genetic Diagnostic Laboratory, University of Pennsylvania
Department: Genetics

Contact information
415 Anatomy Chemistry Building
3620 Hamilton Walk
Philadelphia, PA 19104
Office: 215-898-3122
Fax: 215-573-5940
Lab: 215-573-3020
Education:
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 Itmat Expertise

Dr. Ganguly focuses on the genomics of ocular tumors, specifically, retinoblastoma and uveal melanoma, translating basic science findings to clinical molecular genetic tests.

Selected Publications

McEvoy Justina, Nagahawatte Panduka, Finkelstein David, Richards-Yutz Jennifer, Valentine Marcus, Ma Jing, Mullighan Charles, Song Guangchun, Chen Xiang, Wilson Matthew, Brennan Rachel, Pounds Stanley, Becksfort Jared, Huether Robert, Lu Charles, Fulton Robert S, Fulton Lucinda L, Hong Xin, Dooling David J, Ochoa Kerri, Mardis Elaine R, Wilson Richard K, Easton John, Zhang Jinghui, Downing James R, Ganguly Arupa, Dyer Michael A: RB1 gene inactivation by chromothripsis in human retinoblastoma. Oncotarget Jan 2014.

Chen Zhao, Moran Kimberly, Richards-Yutz Jennifer, Toorens Erik, Gerhart Daniel, Ganguly Tapan, Shields Carol L, Ganguly Arupa: Enhanced Sensitivity for Detection of Low-Level Germline Mosaic RB1 Mutations in Sporadic Retinoblastoma Cases Using Deep Semiconductor Sequencing. Human mutation 35(3): 384-91, Nov 2013.

Ewens Kathryn G, Kanetsky Peter A, Richards-Yutz Jennifer, Al-Dahmash Saad, De Luca Maria Carla, Bianciotto Carlos G, Shields Carol L, Ganguly Arupa: Genomic profile of 320 uveal melanoma cases: chromosome 8p-loss and metastatic outcome. Investigative ophthalmology & visual science 54(8): 5721-9, Aug 2013.

Abdolahi Amir, van Wijngaarden Edwin, McClean Michael D, Herrick Robert F, Allen Joe G, Ganguly Arupa, Bunin Greta R: A case-control study of paternal occupational exposures and the risk of childhood sporadic bilateral retinoblastoma. Occupational and environmental medicine 70(6): 372-9, Jun 2013.

Bunin Greta R, Li Yimei, Ganguly Arupa, Meadows Anna T, Tseng Marilyn: Parental nutrient intake and risk of retinoblastoma resulting from new germline RB1 mutation. Cancer causes & control : CCC 24(2): 343-55, Feb 2013.

Pinney Sara E, Ganapathy Karthik, Bradfield Jonathan, Stokes David, Sasson Ariella, Mackiewicz Katarzyna, Boodhansingh Kara, Hughes Nkecha, Becker Susan, Givler Stephanie, Macmullen Courtney, Monos Dimitrios, Ganguly Arupa, Hakonarson Hakon, Stanley Charles A: Dominant form of congenital hyperinsulinism maps to HK1 region on 10q. Hormone research in pædiatrics 80(1): 18-27, 2013.

Bunin Greta R, Tseng Marilyn, Li Yimei, Meadows Anna T, Ganguly Arupa: Parental diet and risk of retinoblastoma resulting from new germline RB1 mutation. Environmental and molecular mutagenesis 53(6): 451-61, Jul 2012.

Macmullen Courtney M, Zhou Qing, Snider Kara E, Tewson Paul H, Becker Susan A, Aziz Ali Rahim, Ganguly Arupa, Shyng Show-Ling, Stanley Charles A: Diazoxide-unresponsive congenital hyperinsulinism in children with dominant mutations of the β-cell sulfonylurea receptor SUR1. Diabetes 60(6): 1797-804, Jun 2011.

Bunin Greta R, Felice Marc A, Davidson William, Friedman Debra L, Shields Carol L, Maidment Andrew, O'Shea Michael, Nichols Kim E, Leahey Ann, Dunkel Ira J, Jubran Rima, Rodriguez-Galindo Carlos, Schmidt Mary Lou, Weinstein Joanna L, Goldman Stewart, Abramson David H, Wilson Matthew W, Gallie Brenda L, Chan Helen S L, Shapiro Michael, Cnaan Avital, Ganguly Arupa, Meadows Anna T: Medical radiation exposure and risk of retinoblastoma resulting from new germline RB1 mutation. International journal of cancer. Journal international du cancer 128(10): 2393-404, May 2011.

Shields Carol L, Ramasubramanian Aparna, Ganguly Arupa, Mohan Diwakar, Shields Jerry A: Cytogenetic testing of iris melanoma using fine needle aspiration biopsy in 17 patients. Retina (Philadelphia, Pa.) 31(3): 574-80, Mar 2011.

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Last updated: 04/10/2014
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