• Dunham, Christopher

    Investigator, BC Children's Hospital

    Clinical Associate Professor, Department of Pathology and Laboratory Medicine, University of British Columbia

    Degrees / Designations
    BSc, MD
    Primary Area of Research
    Childhood Diseases
    Secondary Area(s) of Research
    Lab Phone
    Mailing Address

    Shaughnessy Building
    Room L218
    4500 Oak St.
    Vancouver, BC V6H 3N1

    Affiliate Websites
    Research Areas
    • Pediatric Brain Neoplasia
    • CNS Malformations
    • Hypoxic Ischemic Injury

    As a pediatric Neuropathologist, I am charged with the diagnosis and study of diseases of the nervous system in children. I examine abnormal tissues that are sampled from patients undergoing surgery or autopsy. These clinically derived tissues form the basis of my laboratory based practice and largely guide my research.  Chiefly via microscopy, I am able to distinguish the culprit disease process(es) that is(are) affecting a patient; in turn, this information is then relayed to the primary care clinicians (eg, neurologists, neurosurgeons, oncologists etc.) and used to guide patient care.

    One form of brain cancer has particularly captured my attention: Atypical Teratoid Rhabdoid Tumor (ATRT). My research into ATRT is aimed at re-examining BCCH’s experience with this tumor and using this information to guide the treatment of future patients. In addition, in a BCCH Telethon funded project, I am investigating the microscopy and genetics of Anencephaly, most common congenital brain malformation which is considered to reside amongst the ‘neural tube disorders’.

    Current Projects

    “Atypical Teratoid Rhabdoid Tumour” (ATRT) is relatively rare and deadly form of brain cancer that primarily occurs in children less than 2 years old.  Despite intensive treatment, most patients only survive 1 year. Until recently, ATRTs were notoriously difficult to diagnose. Armed with a new diagnostic immunohistochemical test called INI-1, my colleagues and I set out to reassess the past incidence of ATRT at BCCH.

    Amongst 10 previously unrecognized cases of ATRT in our pathology archives, we identified 3 rare long term survivors. Recently, colleagues at the University of Colorado in Denver discovered a new sensitive marker of ATRTs called claudin-6. Claudin-6 appears specifically overexpressed in ATRT as opposed to other central nervous system tumours. In collaboration with our American colleagues, we found that 11 of our 15 BCCH ATRTs stained positively with claudin-6. Interestingly, amongst the 4 negative cases were all three of our long term survivors. As such, we proposed that claudin-6 may also act as a prognostic marker, wherein immunohistochemical positivity identifies patients likely to incur a poor outcome. Currently, we are attempting to unravel the presumptive biological underpinnings of long term survivorship in ATRT, and in turn translate these findings into improved patient care.

    Anencephaly is the most common congenital brain malformation, affecting up to 1% of all pregnancies. Anencephaly is considered to be one of the “neural tube defects” (NTDs), a group of disorders that involve early faulty closure of the fetal neural tube.  In particular, anencephaly is thought by some to represent a combination of a lack of closure (by 28 days of gestation) of the rostral neural tube and a lack of formation of the skull cap (ie, calvarium). According to this hypothesis, the bony skull defect exposes the open neural tube to toxic amniotic fluid. The developing brain subsequently erodes, leaving behind a mass of residual tissue called the “area cerebrovasculosa” (AC).

    The abundance of autopsy cases at BCCH enticed me to investigate anencephaly more closely. There are no large modern studies that document the microscopic appearance of anencephaly; in particular, an immunohistochemical profile of the “AC” is currently lacking. As such, part of my research  is to elucidate the histology of anencephaly using modern techniques.

    Although the cause of anencephaly is not known, treatment with folic acid has been found to reduce the incidence of NTDs in general. As such, environmental influences appear partially causal in anencephaly. However, familial cases in the literature also point to a genetic component to anencephaly. Unfortunately, a putative genetic defect is yet to be discovered. In a large series, Norman et al. (1995) stated that routine cytogenetic analysis of anencephaly often reveals a normal chromosomal complement.  Using more modern genetic techniques, rare case reports have suggested the potential role for partial chromosome 2p duplication in anencephaly. As such, my colleagues at BCCA and I have sought out to genetically study a large series of anencephalics using single nucleotide polymorphism (ie, SNP) arrays. The SNP platform is a very sensitive technique that can be used to scan the genome (beyond the ability of routine cytogenetics) for characteristic chromosomal abnormalities. Our work is ongoing, and our goal is to uncover any underlying genetic etiology in anencephaly.

    Selected Publications

    Wiltshire K, Dunham C, Auer R et al. Neuronal Intranuclear Inclusion Disease Presenting as Juvenile Parkinsonism. Canadian Journal of the Neurological Sciences, 2010; 37: 213-218. 2010

    Dunham C. Pediatric Brain Tumors: A Histologic and Genetic Update on Commonly Encountered Entities. Diagnostic Seminars in Pathology, 2010; In Press.

    Dunham C. Gliosarcoma. Clinico-pathology, Genetics and a Review of Rare Congenital Cases. European Oncology, 2009; 5(1): 20-24.

    Dunham CP, Curry B, Hamilton M. Malignant transformation of an intraaxial-supratentorial neurenteric cyst - case report and review of the literature. Clin Neuropathol. 2009 Nov-Dec;28(6):460-6.

    Hocwald O, McFadden D, Osiovich H, Dunham C. Congenital gliosarcoma: detailed clinicopathologic documentation of a rare neoplasm. Pediatr Dev Pathol. 2009 Sep-Oct;12(5):398-403.

    Dunham C, Hussong J, Seiff M, Pfeifer J, Perry A.  Primary intracerebral angiomatoid fibrous histiocytoma: report of a case with a t(12;22)(q13;q12) causing type 1 fusion of the EWS and ATF-1 genes.  Am J Surg Pathol. 2008 Mar;32(3):478-84.

    van Marle G, Antony J, Ostermann H, Dunham C, Hunt T, Halliday W, Maingat F, Urbanowski MD, Hobman T, Peeling J, Power C.  West Nile virus-induced neuroinflammation: glial infection and capsid protein-mediated neurovirulence.   J Virol. 2007 Oct;81(20):10933-49.

    Chacko G, Chacko AG, Dunham CP, Judkins AR, Biegel JA, Perry A.  Atypical teratoid/rhabdoid tumor arising in the setting of a pleomorphic xanthoastrocytoma. J Neurooncol. 2007 Sep;84(2):217-22.

    Dunham C, Sugo E, Tobias V, Wills E, Perry A.  Embryonal tumor with abundant neuropil and true rosettes (ETANTR): report of a case with prominent neurocytic differentiation. J Neurooncol. 2007 Aug;84(1):91-8.

    Miller CR, Dunham CP, Scheithauer BW, Perry A.  Significance of necrosis in grading of oligodendroglial neoplasms: a clinicopathologic and genetic study of newly diagnosed high-grade gliomas. J Clin Oncol.  2006 Dec 1;24(34):5419-26.

    Knerlich-Lukoschus F, Connolly MB, Hendson G, Steinbok P, Dunham C. Clinical, imaging, and immunohistochemical characteristics of focal cortical dysplasia Type II extratemporal epilepsies in children: analyses of an institutional case series. J Neurosurg Pediatr. 2016 Nov 25:1-14. PMID: 27885945. Impact Factor: 1.757

    Torchia J, Golbourn B, Feng S, Ho KC, Sin-Chan P, Vasiljevic A, Norman JD, Guilhamon P, Garzia L, Agamez NR, Lu M, Chan TS, Picard D, de Antonellis P, Khuong-Quang DA, Planello AC, Zeller C, Barsyte-Lovejoy D, Lafay-Cousin L, Letourneau L, Bourgey M, Yu M, Gendoo DM, Dzamba M, Barszczyk M, Medina T, Riemenschneider AN, Morrissy AS, Ra YS, Ramaswamy V, Remke M, Dunham CP, Yip S, Ng HK, Lu JQ, Mehta V, Albrecht S, Pimentel J, Chan JA, Somers GR, Faria CC, Roque L, Fouladi M, Hoffman LM, Moore AS, Wang Y, Choi SA, Hansford JR, Catchpoole D, Birks DK, Foreman NK, Strother D, Klekner A, Bognár L, Garami M, Hauser P, Hortobágyi T, Wilson B, Hukin J, Carret AS, Van Meter TE, Hwang EI, Gajjar A, Chiou SH, Nakamura H, Toledano H, Fried I, Fults D, Wataya T, Fryer C, Eisenstat DD, Scheinemann K, Fleming AJ, Johnston DL, Michaud J, Zelcer S, Hammond R, Afzal S, Ramsay DA, Sirachainan N, Hongeng S, Larbcharoensub N, Grundy RG, Lulla RR, Fangusaro JR, Druker H, Bartels U, Grant R, Malkin D, McGlade CJ, Nicolaides T, Tihan T, Phillips J, Majewski J, Montpetit A, Bourque G, Bader GD, Reddy AT, Gillespie GY, Warmuth-Metz M, Rutkowski S, Tabori U, Lupien M, Brudno M, Schüller U, Pietsch T, Judkins AR, Hawkins CE, Bouffet E, Kim SK, Dirks PB, Taylor MD, Erdreich-Epstein A, Arrowsmith CH, De Carvalho DD, Rutka JT, Jabado N, Huang A. Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors. Cancer Cell. 2016 Dec 12. PMID: 27960086. 

    Michael Cuccione Childhood Cancer Research Program Brain Tumour Grant - Project: “Personalizing the treatment of pediatric medulloblastoma”

    Honours & Awards
    2000- Millennium Scholarship, Government of Canada

    2000- Association of Professors of the University of Ottawa (APUO) Bursary

    1999- Millennium Scholarship, Government of Canada

    1999- Dutkevich Memorial Foundation Scholarship for Study in the field of Pathology, University of Ottawa

    1999- Association of Professors of the University of Ottawa (APUO) Bursary

    1996- Dean’s Honour Roll, First Class Standing, University of Alberta
    Research Group Members