Sharon E. Plon, M.D., Ph.D.
Professor of Molecular and Human Genetics
Professor, Department of Pediatrics; Program in Integrative Molecular and Biomedical Sciences; Human Genome Sequencing Center
Director, Neurofibromatosis Clinic
Director, M.D./Ph.D. Medical Scientist Training Program
Director, Cancer Genetics Clinical Program and Cancer Genetics Research Program, Texas Children's Hospital
B.S., Massachusetts Institute of Technology, 1980
M.D., Ph.D., Harvard University, 1987
Resident, Internal Medicine, University of Washington, 1988
Postdoc, National Cancer Institute, National Institutes of Health, 1990
Fellow, Medical Genetics, Fred Hutchinson Cancer Research Center, University of Washington, 1993
American Board of Medical Genetics: Clinical Genetics
The overall goal of my laboratory is to understand the genetic basis of inherited susceptibility to cancer. At a basic level, we are interested in studying genes that normally control genomic stability and when disrupted lead to the instability seen in cancer cells including chromosome losses and gains or aneuploidy. Disruption of these control mechanisms have been found in a large percentage of human tumors and in individuals with a predisposition to specific cancers.
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 have investigated 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 have now received NHGRI funding to launch a study on the impact of adding whole exome sequencing of tumor and blood into the care of newly diagnosed childhood cancer patients.
- Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Eng CM (2013). Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders. N. Engl. J. Med. [Epub ahead of print] PubMed PMID: 24088041
- Cheung HC, Yatsenko SA, Kadapakkam M, Legay H, Su J, Lupski JR, Plon SE (2012). Constitutional tandem duplication of 9q34 that truncates EHMT1 in a child with ganglioglioma. Pediatr. Blood Cancer 58(5): 801-5. PubMed PMID: 21681934
- Ziogas A, Horick NK, Kinney AY, Lowery JT, Domchek SM, Isaacs C, Griffin CA, Moorman PG, Edwards KL, Hill DA, Berg JS, Tomlinson GE, Anton-Culver H, Strong LC, Kasten CH, Finkelstein DM, Plon SE (2011). Clinically relevant changes in family history of cancer over time. JAMA 306(2): 172-8. PubMed PMID: 21750294
- Hicks S, Wheeler DA, Plon SE, Kimmel M (2011). Prediction of missense mutation functionality depends on both the algorithm and sequence alignment employed. Hum. Mutat. 32(6): 661-8. PubMed PMID: 21480434
- Plon SE, Wheeler DA, Strong LC, Tomlinson GE, Pirics M, Meng Q, Cheung HC, Begin PR, Muzny DM, Lewis L, Biegel JA, Gibbs RA (2011). Identification of genetic susceptibility to childhood cancer through analysis of genes in parallel. Cancer Genet. 204(1): 19-25. PubMed PMID: 21356188
- Plon SE (2011). Unifying cancer genetics. Genet. Med. 13(3): 203-4. PubMed PMID: 21311342
- Poland KS, Shardy DL, Azim M, Naeem R, Krance RA, Dreyer ZE, Neeley ES, Zhang N, Qiu YH, Kornblau SM, Plon SE (2009). Overexpression of ZNF342 by juxtaposition with MPO promoter/enhancer in the novel translocation t(17;19)(q23;q13.32) in pediatric acute myeloid leukemia and analysis of ZNF342 expression in leukemia. Genes Chromosomes Cancer 48(6): 480-9. PubMed PMID: 19255975
- Plon SE, Pirics ML, Nuchtern J, Hicks J, Russell H, Agrawal S, Zbuk K, Eng C, Hegde M, Chin EL (2008). Multiple tumors in a child with germ-line mutations in TP53 and PTEN. N. Engl. J. Med. 359(5): 537-9. PubMed PMID: 18669439
- Shinawi M, Erez A, Shardy DL, Lee B, Naeem R, Weissenberger G, Chinault AC, Cheung SW, Plon SE (2008). Syndromic thrombocytopenia and predisposition to acute myelogenous leukemia caused by constitutional microdeletions on chromosome 21q. Blood 112(4): 1042-7. PubMed PMID: 18487507
- Strome ED, Wu X, Kimmel M, Plon SE (2008). Heterozygous Screen in Saccharomyces cerevisiae Identifies Dosage Sensitive Genes that Impact Chromosome Stability. Genetics 178(3): 1193-207. PubMed PMID: 18245329
Sharon E. Plon, M.D., Ph.D.
Department of Pediatrics, Hematology-Oncology
Baylor College of Medicine
Feigin Center, Suite 1200
1102 Bates Street
Houston, TX 77030, U.S.A.
Phone: 832-824-4251 (Academic Office)