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de la Chapelle, Albert


Department of Cancer Biology and Genetics

Contact Information:


804 Biomedical Research Tower
460 W 12th Ave
Columbus, OH 43210
Phone: (614) 688-4781
Fax: (614) 688-4772
E-Mail: albert.delachapelle@osumc.edu

Research Interests:

Research in Dr. de la Chapelle’s laboratory focuses on the mapping, cloning, and characterization of high- and low-penetrance genes for cancer predisposition.  When new genes are identified, studies are directed to determine the pathophysiological role of the proteins or RNA molecules they encode, and the mechanisms by which mutations in the genes contribute to the cancer phenotype. Finally, there is an emphasis on translational aspects of the research, viz. the exploitation of laboratory discoveries towards new diagnostic and therapeutic procedures.  Diseases under study include colorectal cancer, papillary thyroid cancer, acute myeloid leukemia and chronic lymphocytic leukemia.   Colorectal cancer is highly heritable; but only a fraction of all predisposing genes have been detected so far.  Even so, screening all colorectal and endometrial cancer patients for mutations in the mismatch repair genes (Lynch syndrome) is practically feasible and desirable, because it can save lives through clinical surveillance of targeted high-risk family members.  A method of population-wide screening for Lynch syndrome has been developed and its nationwide use is being encouraged.  In papillary thyroid cancer predisposing germline mutations are sought by a variety of methods, including linkage, allelic association, and the determination of allelic differences in gene expression.  The role of non-coding RNA genes is emerging as a major cause of predisposition to papillary thyroid cancer.  Several novel candidate genes are investigated that predispose to thyroidate genes are investigated that predispose to thyroid cancer. Two long noncoding RNA genes named Papillary Thyroid Carcinoma Susceptibility Candidate 2 (PTCSC2 in chromosome 9q22) and PTCSC3 (in chromosome 14q13) have been identified and implicated.  One single nucleotide variant in an enhancer element located in chromosome 4q32 predisposes to thyroid cancer with apparently high penetrance but is utterly rare.  Finally, a common variant in the pre-miR146a sequence causes low penetrance thyroid cancer predisposition.  A challenge for present and future research is to identify the downstream target genes of these and other sequence variants. Second-generation deep sequencing is replacing previously used methods in the search for deleterious mutations.  In acute myeloid leukemia the group cloned a novel gene, BAALC for Brain and Acute Leukemia, Cytoplasmic that is expressed in early hematopoietic progenitor cells, and in a subset of the acute myeloid and lymphoid leukemias. Ongoing studies aim at understanding the precise role of BAALC in leukemogenesis.  The working hypothesis is that BAALC is a marker of, or even a contributor to, blocked differentiation of these cells. The novel miR-3151 is located in an intron of BAALC and is hypothesized to act as an independent oncogene in AML.  The novel miR-3662 located in a major quantitative trait locus on chromosome 6q23 appears to act as a tumor suppressor that when downregulated conveys AML risk.  In chronic lymphocytic leukemia the role of the proapoptotic gene DAPK1 is investigated, and in families with several affected individuals novel predisposing genes are sought by second-generation deep sequencing. 


MD, University of Helsinki, FI, 1957
PhD, Human Genetics, University of Helsinki, FI, 1962
Internship/Residency: University of Helsinki, FI, 1965
Postdoctoral Training: Biochemistry, Columbia University, 1968
Subspecialty Training: University of Helsinki, FI, 1965, 1986
Training: Molecular Genetics, Institute of Molecular Pathology, Paris, France, 1981


Selected Publications

For current publications please visit The National Center for Biotechnology Information's PubMed website at http://www.ncbi.nlm.nih.gov/pubmed?term=de%20la%20Chapelle%20A

Aaltonen LA, Salovaara R, Kristo P, Canzian F, Hemminki A, Peltomäki P, Chadwick RB, Kääriänen H, Percesepe A, Ahtola H, Härkönen N, Julkunen R, Kangas E, Ojala S, Tulikoura J, Valkamo E, Eskelinen M, Järvinen H, Mecklin JP, de la Chapelle A: Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. New Engl J Med 338:1481-1487, 1998

Tanner SM, Austin JL, Leone G, Rush LJ, Plass C, Heinonen K, Mrozek K, Sill H, Knuutila S, Kolitz JE, Archer KJ, Caligiuri MA, Bloomfield CD, de la Chapelle A: BAALC, the human member of a novel mammalian neuroectoderm gene lineage, is implicated in hematopoiesis and acute leukemia. Proc Natl Acad Sci USA 98:13901-13096, 2001

Huang Y, Prasad M, Lemon WJ, Hampel H, Wright FA, Kornacker K, LiVolsi V, Frankel W, Kloos RT, Eng C, Pellegata NS, de la Chapelle A: Gene expression in papillary thyroid carcinoma reveals highly consistent profiles. Proc Natl Acad Sci USA 98:15044-15049, 2001

Tanner SM, Aminoff M, Wright FA, Liyanarachchi S, Kuronen M, Saarinen A, Massika O, Mandel H, Broch H, de la Chapelle A: Amnionless, essential for mouse gastrulation, is mutated in recessive hereditary megaloblastic anemia. Nature Genet 33:426-429, 2003

Lynch HT, Coronel SM, Okimoto R, Hampel H, Sweet K, Lynch JF, Barrows A, Wijnen J, van der Klift H, Franken P, Wagner A, Fodde R, de la Chapelle A: A founder mutation of the MSH2 gene and hereditary nonpolyposis colorectal cancer in the United States. JAMA 291:718-724, 2004

Baldus CD, Liyanarachchi S, Mrozek K, Auer H, Tanner SM, Guimond M, Ruppert AS, Mohamed N, Davuluri RV, Caligiuri MA, Bloomfield CD, de la Chapelle A: Acute myeloid leukemia with complex karyotypes and abnormal chromosome 21:amplification discloses overexpression of APP, ETS2 and ERG genes, PNAS 101:3915-3920, 2004

Tanner SM, Li Z, Perko JD, Oner C, Cetin M, Altay C, Yurtsever Z, David KL, Faivre L, Ismail EA, Grasbeck R, de la Chapelle A: Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene. Proc Natl Acad Sci U S A. 102:4130-4133, 2005

Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, Panescu J, Fix D, Lockman J, Comeras I, de la Chapelle A: Screening for the Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) New Engl J Med 352:1851-1860, 2005

He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, Calin GA, Liu C-G, Franssila K, Suster S, Kloos RT, Croce CM, de la Chapelle A: The role of micro-RNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA 102:19075-19080, 2005

Hampel H, Frankel W, Panescu J, Lockman J, Sotamaa K, Fix D, Comeras I, LaJeunesse J, Nakagawa H, Westman JA, Prior TW, Clendenning M, Penzone P, Lombardi J, Dunn P, Cohn D, Copeland L, Eaton L, Fowler J, Lewandowski G, Vaccarello L, Bell J, Reid G, de la Chapelle A: Screening for Lynch Syndrome (HNPCC) among endometrial cancer patients. Cancer Res 66:7810-7817, 2006

Raval A, Tanner S, Byrd J, Angerman E, Perko J, Chen S-S, Grever M, Lucas D, Matkovic J, Lin T, Kipps T, Murry F, Weisenburger D, Sanger W, Lynch J, Watson P, Jansen M, Yoshinaga Y, Rosenquist R, de Jong P, Coggill P, Beck S, Lynch H, de la Chapelle A, Plass C: Down-regulation of death associated protein kinase 1 (DAPK1) in chronic lymphocytic leukemia. Cell 129:879-890, 2007
Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Clendenning M, Sotamaa K, Prior T, Westman JA, Panescu J, Fix D, Lockman J, Lajeunesse J, Comeras I, de la Chapelle A.  Feasibility of Screening for Lynch Syndrome Among Patients With Colorectal Cancer.  J Clin Oncol. 26:5783-5788, 2008

Bonafé L, Hastbacka J, de la Chapelle A, Campos-Xavier AB, Chiesa C, Forlino A, Superti-Furga A, Rossi A.  A novel mutation in the sulphate transporter gene SLC26A2 (DTDST) specific to the Finnish population causes de la Chapelle dysplasia.  J Med Genet. 45:827-831, 2008

Valle L, Serena-Acedo T, Liyanarachchi S, Hampel H, Comeras I, Li Z, Zeng Q, Zhang HT, Pennison MJ, Sadim M, Pasche B, Tanner SM, de la Chapelle A. Germline allele-specific expression of TGFBR1 confers an increased risk of colorectal cancer. Science  321(5894):1361-1365, 2008

Jazdzewski K, Liyanarachchi S, Swierniak M, Pachucki J, Ringel MD, Jarzab B, de la Chapelle A: Polymorphic mature micro RNAs from passenge rstrand of pre-miR-146a contribute to thyroid cancer.  PNAS 106:1502-1505, 2009

Gudmundsson J, Sulem P, Gudbjartsswon DF, Jonasson JG, Sigurdsson A, Bergthorsson JT, He H, Blondal T, Geller F, Jakobsdottir M, Magnusdottir DN, Matthiasdottir S, Stacey SN, Skarphedinsson OB, Helgadottir H, Li W, Nagy R, Aguillo E, Faure E, Prats E, Saez B, Martinez M, Eyjolfsson GI, Bjornsdottir US, Holm H, Kristjansson K, Frigge ML, Kristvinsson H, Gulcher JR, Jonsson T, Rafnar T, Hjartarson H, Mayordomo JI, de la Chpaelle A, Hrafnkelsson J, Thorsteinsdottir U, Kong A, Stefansson K: Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations.  Nature Genet 41:460-464, 2009

de la chapelle A, Hampel H: Clinical relevance of Microsatellite instabiity in colorectal cancer.  J Clin Oncol 28:3380-3387, 2010

He H, Liyanarachchi S, Akagi K, Nagy R, Li J, Dietrich RC, Li W, Sebastian N, Wen B, Xin B, Singh J, Yan P, Alder H, Haan E, Wieczorek D, Albrecht B, Puffenberger E, Wang H, Westman JA, Padgett RA, Symer DE, de la Chapelle A: Mutations in U4atac snRNA, a component of the minor Spliceosome, in the developmental disorder MOPD1. Science 332:238-240, 2011 www.sciencemag.org/cgi/rapidpdf/332/6026/238