Integrative Tumor Epidemiology Branch Research Areas
Listed below is an overview of the research conducted within the Integrative Tumor Epidemiology Branch (ITEB) by both research approach and malignancy.
Research conducted by ITEB investigators involves:
- Designing, conducting and analyzing molecular epidemiology studies with tissue collections;
- Characterizing tumors using morphology, histopathology, and immunohistochemistry/in situ hybridization staining and scoring of tissue slides from formalin-fixed paraffin embedded (FFPE) or fresh frozen (FF) material;
- Molecular profiling of tumors, including genomic analyses conducted at the DCEG Cancer Genomics Research (CGR) Laboratory and external laboratories;
- Designing and utilizing large-scale analytic tools for integrated data analytics of high dimensional, complex data;
- Using publicly available data from resources such as the The Cancer Genome Atlas (TCGA), ENCODE and Genotype-Tissue Expression (GTEx) projects, and the International Cancer Genome Consortium (ICGC);
- Participating and contributing to large national and international consortia.
Major Research by Malignancy
Investigators in ITEB seek to elucidate molecular mechanisms underlying breast carcinogenesis and etiologic heterogeneity of breast cancers through integrative molecular epidemiology studies. ITEB researchers are active in the Breast CAncer STratification (BCAST) Project, the Confluence Project, and additionally maintain a large portfolio of breast cancer studies, including:
- molecular epidemiology of mammographic density, one of the strongest risk factors for breast cancer;
- morphologic features of terminal duct lobular units (TDLUs) in non-malignant breast tissue in relation to breast cancer risk;
- genome-wide association studies (GWAS) of breast cancer subtypes; somatic profiling of tumors in relation to germline and environmental exposures in different populations (European, Asian, and African ancestry);
- interrelation of genetic and environmental risk factors, tumor features, and clinical progression using targeted DNA sequencing and immunohistochemistry and in-situ hybridization analysis of thousands of breast tumors in the international consortium
ITEB investigators study chordoma in families to 1) identify the mutated or altered genes that cause familial chordoma, and 2) determine whether chordoma-prone families are at increased risk of other cancers. They also explore whether genes associated with familial chordoma play a role in sporadic chordoma, the development of chordoma in those who lack family history of the malignancy.
Investigators have identified germline duplication of the T gene as a major susceptibility mechanism in some chordoma families, and through subsequent analyses have identified multiple common and rare T variants associated with chordoma risk. Studies seeking to identify additional susceptibility genes in chordoma families are ongoing.
ITEB investigators are studying inherited genetic variation to identify regions in the genome associated with increased risk of Ewing Sarcoma (EWS). To achieve this aim, they compare the frequency of genotyped genetic variants between EWS cases and ancestry-matched, cancer-free controls.
While relatively little is known about the mechanisms that initiate and select for mosaic alterations, ITEB researchers have found evidence suggesting that genetic mosaicism increases cancer risk for hematologic malignancies and select solid tumor subtypes. Ongoing research continues to examine the influence of mosaicism on cancer risk in special exposure populations and various tissue types.
Read the latest research on genetic mosaicism.
A suite of web-based applications created by ITEB investigators to easily and efficiently interrogate linkage disequilibrium in populations.
ITEB investigators are conducting studies to characterize renal cell carcinoma uncommon histological subtypes. These studies utilize whole-genome sequencing, deep target sequencing, whole genome methylation, and SNP array analyses.
ITEB investigators study the genetic and environmental determinants of lung cancer using an integrative approach that allows them to explore the process that begins with smoking initiation and persistence, continues with lung cancer development, and ends with progression to disseminated disease or response to therapy and survival. Investigators use data from a large population-based case-control study in the Lombardy region of Italy, called the Environment And Genetics in Lung cancer Etiology (EAGLE) study.
Sherlock-Lung, a comprehensive study spearheaded by DCEG investigators, further aims to trace the etiology of lung cancer in never smokers (LCINS). To characterize the genomic landscape of LCINS and to identify exogenous and endogenous processes involved in lung tumorigenesis, researchers are analyzing whole genome sequencing, whole transcriptome, genome-wide methylation, and microbiome data. The molecular landscape will be integrated with histological and radiological features to develop a more refined classification of LCINS and to provide insights into prognosis and treatment strategies.
Converging lines of evidence suggest that melanoma comprises biologically distinct subtypes. DCEG investigators are undertaking tissue-based and genomic studies to provide a comprehensive classification of primary melanomas and the molecular changes associated with metastatic potential.
Melanoma studies focused on specific populations are also underway. These include:
- MelaNostrum Consortium studies of melanoma risk and progression in Mediterranean populations
- studies seeking to identify new genes associated with melanoma susceptibility in melanoma-prone families