We have developed a multidisciplinary program to investigate genetic events leading to childhood cancer using genetic epidemiologic, cellular, and molecular techniques. The hypotheses are based-on a multi-stage model for cancer, and are tested in two model childhood and adolescent cancers, sarcomas and Wilms' tumor of the kidney. For each tumor type, there are specific genes that have been identified that may be altered both as germline mutations and as tumor-specific mutations. There is also significant evidence for genetic heterogeneity in the etiology of each tumor. The underlying themes of the program include characterizing the tumor types with respect to a multi-stage model, determination of the heritable contribution to each tumor, analysis of germline and somatic mutations by type and mechanism, and determination of the implications of germline mutations for the patients and their families. The findings from this program should provide insights into the mechanisms of carcinogenesis as well as guidelines for clinical programs for patients at high risk of cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA034936-09A1
Application #
3093586
Study Section
Special Emphasis Panel (SRC (E1))
Project Start
1984-07-01
Project End
1998-07-31
Budget Start
1993-09-09
Budget End
1994-07-31
Support Year
9
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
Other Domestic Higher Education
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Peng, Gang; Bojadzieva, Jasmina; Ballinger, Mandy L et al. (2017) Estimating TP53 Mutation Carrier Probability in Families with Li-Fraumeni Syndrome Using LFSPRO. Cancer Epidemiol Biomarkers Prev 26:837-844
Maturu, Paramahamsa; Jones, Devin; Ruteshouser, E Cristy et al. (2017) Role of Cyclooxygenase-2 Pathway in Creating an Immunosuppressive Microenvironment and in Initiation and Progression of Wilms' Tumor. Neoplasia 19:237-249
Huang, Le; Mokkapati, Sharada; Hu, Qianghua et al. (2016) Nephron Progenitor But Not Stromal Progenitor Cells Give Rise to Wilms Tumors in Mouse Models with ?-Catenin Activation or Wt1 Ablation and Igf2 Upregulation. Neoplasia 18:71-81
Palculict, Timothy Blake; Ruteshouser, E Cristy; Fan, Yu et al. (2016) Identification of germline DICER1 mutations and loss of heterozygosity in familial Wilms tumour. J Med Genet 53:385-8
Liu, Changlu; Ma, Jianzhong; Amos, Christopher I (2015) Bayesian variable selection for hierarchical gene-environment and gene-gene interactions. Hum Genet 134:23-36
Mokkapati, Sharada; Niopek, Katharina; Huang, Le et al. (2014) ?-catenin activation in a novel liver progenitor cell type is sufficient to cause hepatocellular carcinoma and hepatoblastoma. Cancer Res 74:4515-25
Quintás-Cardama, Alfonso; Post, Sean M; Solis, Luisa M et al. (2014) Loss of the novel tumour suppressor and polarity gene Trim62 (Dear1) synergizes with oncogenic Ras in invasive lung cancer. J Pathol 234:108-19
Maturu, Paramahamsa; Overwijk, Willem W; Hicks, John et al. (2014) Characterization of the inflammatory microenvironment and identification of potential therapeutic targets in wilms tumors. Transl Oncol 7:484-92
Shahidul Makki, Mohammad; Cristy Ruteshouser, E; Huff, Vicki (2013) Ubiquitin specific protease 18 (Usp18) is a WT1 transcriptional target. Exp Cell Res 319:612-22
Kaftanovskaya, Elena M; Neukirchner, Giselle; Huff, Vicki et al. (2013) Left-sided cryptorchidism in mice with Wilms' tumour 1 gene deletion in gubernaculum testis. J Pathol 230:39-47

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