Sharon E. Plon, MD, PhD, FACMG
On a more translational level, we have carried out analyses of a variety of autosomal recessive cancer predisposition syndromes. Rothmund-Thomson Syndrome (RTS) is associated with a high incidence of osteosarcoma. We have determined that RTS patients who develop osteosarcoma carry deleterious mutations in the RECQL4 gene and we have identified that certain disease causing mutations are associated with mislocalization of the RECQL4 protein (Wang, JNCI, 2003; Burks, GENE, 2009).
Most recently, we initiated a project in collaboration with the Human Genome Sequencing Center to develop a large-scale sequencing to identify the causative mutation or chromosome imbalance in families with unusual patterns of childhood cancer. The initial pipeline based on Sanger sequencing analyzed coding regions of 45 cancer-associated genes from genomic DNA of families that have multiple children with cancer or a child with more then one cancer diagnosis (Plon, Cancer Genetics, 2011).
We are also using high density oligonucleotide arrays to identify regions of copy number variation in children with cancer and congenital anomalies or learning problems (Cheung, Pediatric Blood and Cancer, 2011). We have now expanded this study to perform whole exome and whole genome analyses of cohorts of families with similar cancer patterns, for example, families with predisposition to childhood acute lymphocytic leukemia and lymphoma. This is a highly collaborative project with collaborators including: Human Genome Sequencing Center, MD Anderson Cancer Center and the Department of Statistics at Rice University.
I am also involved in clinical research. We are currently investigating how physicians who do not have genetics training utilize genetic testing in their clinical practice to aid patients at increased risk of cancer (Plon, 2011; Dhar, 2011). We will expand this to physician interpretation of clinical whole exome data of newly diagnosed childhood cancer patients in early 2012.