Joint Analysis of Germline and Cancer Genomes in a High-Risk CLL Pedigree

Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the US with an incidence of 14,990 new cases each year. The large majority of these patients - 69 to 79 percent - will eventually die from their disease. New approaches to treating CLL will come from a better understanding of how the cancer arises, and how it progresses toward aggressive stages.     

Even though there is strong evidence that CLL runs in families, the genetic risk factors that predispose individuals toward the disease remain unknown. Nicola Camp, Ph.D., professor of internal medicine, has identified 400 families within the Utah Population Database who are at high-risk for developing CLL, proving it as a rich resource for understanding the genetics behind the disease.

Camp is collaborating with Mark Yandell, Ph.D., professor of human genetics, to perform cutting-edge genomic analyses in one high-risk family to tease apart the genetics of CLL at different stages. They are performing whole genome sequencing of patient germline DNA – the DNA that is inherited from parents – to identify genetic changes that predispose individuals to developing CLL. In tandem, they are sequencing DNA isolated from tumors. A signature of cancer is that DNA within tumor cells rapidly acquires new mutations, some of which drive disease progression. Determining when and where changes in tumor DNA occur can provide information on the stage, severity, and type of cancer that an individual has.

Analyzing germline and cancer DNA in parallel can provide answer to such questions as: Are distant relatives who have CLL born with the same genetic risk factors? Do their tumors accumulate the same genetic mutations as the disease progresses? Answering such questions will identify patterns of inheritance and disease progression that will advance not only the understanding of CLL, but also fuel development of software for analyzing cancer genomes.