Sharon A. Savage, M.D.
Clinical Genetics Branch
9609 Medical Center Drive
Rockville, MD 20850
Telomere Molecular Epidemiology
Telomeres, specialized structures consisting of long DNA nucleotide repeats and a protein complex, are designed to protect the ends of chromosomes and are critical to chromosome stability. Each time a cell divides, the telomeres lose a small amount of DNA and become shorter. Eventually, telomeres become critically short, causing cellular senescence or cellular crisis, which result in apoptosis, genomic instability or a reduction in cellular lifespan. If cells bypass natural processes and continue to divide despite the presence of genomic instability, cancer can develop. Dr. Savage investigates the connection between telomere biology and cancer through studies of the association between telomere length and cancer risk, the telomere biology disorder dyskeratosis congenita, and the genetic contribution to telomere biology.
Li-Fraumeni syndrome (LFS) is a highly-penetrant autosomal dominant cancer predisposition syndrome associated with a wide range of cancer types which occur at younger-than-expected ages. It was first described in 1969 and germline mutations in TP53 were recognized as the primary cause in 1990. Dr. Savage and her colleagues have initiated a new clinical, genetic, and epidemiologic study of LFS in order to further characterize the clinical and molecular consequences of this disorder, and to develop a cancer screening program for TP53 mutation carriers (www.lfs.cancer.gov). They also assisted in the creation of an international LFS research consortium.
Dr. Savage joined the Clinical Genetics Branch, DCEG, NCI in 2006 as a tenure-track investigator. She was awarded scientific tenure by the NIH and appointed senior investigator in 2012. In 2013, she was promoted to Branch Chief. Dr. Savage received her M.D. from the University of Vermont College of Medicine, completed residency training in Pediatrics at Children’s National Medical Center, in Washington DC, and a fellowship in Pediatric Hematology/Oncology at the NCI Pediatric Oncology Branch and Johns Hopkins University. She is board-certified in both Pediatrics and Pediatric Hematology-Oncology.
Dr. Savage is the NCI Liaison to the American Academy of Pediatrics Committee on Environmental Health, and is an elected member of the American Society for Clinical Investigation.
Kocak H, Ballew BJ, Bisht K, Eggebeen R, Hicks BD, Suman S, O'Neil A, Giri N, NCI DCEG Cancer Genomics Research Laboratory., NCI DCEG Cancer Sequencing Working Group., Maillard I, Alter BP, Keegan CE, Nandakumar J, Savage SA. Hoyeraal-Hreidarsson syndrome caused by a germline mutation in the TEL patch of the telomere protein TPP1. Genes Dev. 2014;28(19):2090-102.
Ballew BJ, Yeager M, Jacobs K, Giri N, Boland J, Burdett L, Alter BP, Savage SA. Germline mutations of regulator of telomere elongation helicase 1, RTEL1, in Dyskeratosis congenita. Hum Genet. 2013;132(4):473-80.
Savage SA, Mirabello L, Wang Z, Gastier-Foster JM, Gorlick R, Khanna C, Flanagan AM, Tirabosco R, Andrulis IL, Wunder JS, Gokgoz N, Patiño-Garcia A, Sierrasesúmaga L, Lecanda F, Kurucu N, Ilhan IE, Sari N, Serra M, Hattinger C, Picci P, Spector LG, Barkauskas DA, Marina N, de Toledo SR, Petrilli AS, Amary MF, Halai D, Thomas DM, Douglass C, Meltzer PS, Jacobs K, Chung CC, Berndt SI, Purdue MP, Caporaso NE, Tucker M, Rothman N, Landi MT, Silverman DT, Kraft P, Hunter DJ, Malats N, Kogevinas M, Wacholder S, Troisi R, Helman L, Fraumeni JF Jr, Yeager M, Hoover RN, Chanock SJ. Genome-wide association study identifies two susceptibility loci for osteosarcoma. Nat Genet. 2013;45(7):799-803.
Mirabello L, Koster R, Moriarity BS, Spector LG, Meltzer PS, Gary J, Machiela MJ, Pankratz N, Panagiotou OA, Largaespada D, Wang Z, Gastier-Foster JM, Gorlick R, Khanna C, de Toledo SR, Petrilli AS, Patiño-Garcia A, Sierrasesúmaga L, Lecanda F, Andrulis IL, Wunder JS, Gokgoz N, Serra M, Hattinger C, Picci P, Scotlandi K, Flanagan AM, Tirabosco R, Amary MF, Halai D, Ballinger ML, Thomas DM, Davis S, Barkauskas DA, Marina N, Helman L, Otto GM, Becklin KL, Wolf NK, Weg MT, Tucker M, Wacholder S, Fraumeni JF Jr, Caporaso NE, Boland JF, Hicks BD, Vogt A, Burdett L, Yeager M, Hoover RN, Chanock SJ, Savage SA. A Genome-Wide Scan Identifies Variants in NFIB Associated with Metastasis in Patients with Osteosarcoma. Cancer Discov. 2015;5(9):920-31.
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This page was last updated on February 7th, 2019