Children's - Hematology-Oncology Hamon Center for Therapeutic Oncology McDermott Center for Human Growth Development Simmons Comprehensive Cancer Center
My laboratory interests are in 1) genetic factors influencing childhood cancer risk 2) the genetic predisposition to breast cancer, including families with BRCA1, BRCA2. In the area of pediatric cancers, I have focused in the laboratory primarily on hepatoblastoma and rhabdoid tumors. We recently reported on two genetic polymorphisms which influence the risk of hepatoblastoma the myeloperoxidase gene, variation of which influences relative risk and the cyclin D1 gene, variation of which influences the age of onset. We have also recently characterized translocations involving chromosome 1q12 breakpoints in hepatoblastoma and have identified a novel developmental pathway involved in this tumor type. In the area of rhabdoid tumor, we recently genetically characterized infants with double primary tumors of the kidney and brain. We also recently completed a genome-wide search for other areas of loss of heterozygosity in rhabdoid tumors of the kidney, many of which were known to have germline hSNF5/INI1 mutations. We observed few overall genomic changes in rhabdoid tumors suggesting that these tumors may not require additional genetic events. In the area of breast cancer, my group in collaboration with Dr. Adi Gazdar, has worked to develop and characterize two tumor cell lines deficient in BRCA1. The first cell line HCC1937 is derived from a BRCA1-5382insC mutation carrier. This cell line has been used by many laboratories to characterize the function of BRCA1. The second cell line, HCC3153 derives from a carrier of the African American founder mutation BRCA1-943ins10. We are currently looking at the role of genetic modifiers in refinement of breast cancer risk in BRCA1 and BRCA2 families.
RESEARCH INTERESTS
Cancer genetic predisposition, risk assessment and counseling
Molecular and cytogenetics of genetics of childhood liver and renal tumors
BRCA1 and BRCA2 related familial breast cancer
Population specific approaches to cancer risk assessment and counseling
RECENT PUBLICATIONS
Swinney RM, Hsu SC, Hirschman BA, Chen TTC, Tomlinson GE, "MDM2 promoter variation and age of diagnosis of acute lymphoblastic leukemia" Leukemia, 19:1996-8, 2005
Tomlinson GE, Breslow NE, Dome J, Gurthrie KA, Norkool P, Li S, Thomas PRM, Perlman E, Beckwith JBB, D’Angio GJ, Green DM, "Rhabdoid tumor of the kidney in the National Wilms Tumor Study: Age at diagnosis as a prognostic factor" J. Clinical Oncology, 23:7641-5, 2005
Tomlinson GE, Douglass IC, Pollock BH, Finegold MJ, Schneider NR, "Cytogenetic analysis of a large series of hepatoblastomas; numerical aberrations with recurring translocations involving 1q12-21" Genes, Chromosomes and Cancer, 44:177-84, 2005
Hirschman BA, Pollock BH, Tomlinson GE, "The spectrum of APC mutations in children with hepatoblastoma from familial adenomatous polyposis kindreds" J. Pediatrics, 147:263-6, 2005
Patterson A, Robinson L, Naftalis E, Haley B, Tomlinson GE, "Custodianship of genetic information: clinical challenges and professional responsibility" J. Clinical Oncology, 23:2100-2104, 2005
SIGNIFICANT PUBLICATIONS
Pakakasama S, Chen T, Frawley W, Lee R, Muller C, Pollock BH, Tomlinson GE, "Cyclin D1 polymorphism and age of onset of hepatoblastoma" Oncogene, 23:4789-92, 2004
Pakakasama S, Chen T, Frawley W, Muller C, Douglass EC, "Variation in the myeloperoxidase gene and risk of hepatoblastoma" International J. Cancer, 106:205-7, 2003
Euhus DM, Smith KC, Robinson L, Stucky FA, Olopade OI, Cummings S, Garger JE, Chittendon A, Mills GB, Reiger P, Esserman L, Crawford B, Hughes KS, Roche C, Ganz P, Sheldon J, Fabian CJ, Klemp J, Tomlinson G, "Pretest prediction of BRCA1 or BRCA2 mutation by risk counselors and the computer model BRCAPRO." J. Natl Cancer Institute, 94:1583-4, 2002
Savla J, Chen T, Schneider NR, Timmons C, Delattre O, Tomlinson G, "Mutation of the hSNF5/INI1 gene in renal rhabdoid tumors with second primary brain tumors" J. Natl Cancer Institute, 92:648-650
Tomlinson GE, Chen TL, Stastny VA, Virmani A, Spillman MA, Tonk VJ, Blum JL, Schneider NJ, Wistuba I, Minna JD, Gazdar AF, "Characterization of a breast cancer cell line derived from a germ-line BRCA1 carrier" Cancer Research, 58:1605-1608, 1998
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