Overview

My current research focuses on exploring chromosome abnormalities in patients diagnosed with acute leukemia.

Acute leukemia is the most common cancer affecting children. Although the outcome of treatment has improved substantially in recent decades, there remains approximately 20 per cent of children treated for leukemia who relapse and have a poor prognosis.

My research aims to use high resolution microarray analysis to better identify the genetic changes associated with acute leukemia. I am particularly interested in determining if there are genetic alterations unique to treatment-resistant leukemia. Obtaining a detailed understanding of the genetics of acute leukemia will enable other researchers to develop targeted, personalized treatments with greater success rates and less harmful effects.

Publications

Vitamin D-binding protein deficiency and homozygous deletion of the GC gene
New England Journal of Medicine
Henderson, C.M. and Fink, S.L. and Bassyouni, H. and Argiropoulos, B. and Brown, L. and Laha, T.J. and Jackson, K.J. and Lewkonia, R. and Ferreira, P. and Hoofnagle, A.N. and Marcadier, J.L.
DOI: 10.1056/NEJMoa1807841
2019

Expanding the FANCO/RAD51C associated phenotype: Cleft lip and palate and lobar holoprosencephaly, two rare findings in Fanconi anemia
European Journal of Medical Genetics
Jacquinet, A. and Brown, L. and Sawkins, J. and Liu, P. and Pugash, D. and Van Allen, M.I. and Patel, M.S.
DOI: 10.1016/j.ejmg.2017.12.011
2018

Genomic and cytogenetic characterization of a balanced translocation disrupting NUP98
Cytogenetic and Genome Research
Thibodeau, M.L. and Steinraths, M. and Brown, L. and Zong, Z. and Shomer, N. and Taubert, S. and Mungall, K.L. and Ma, Y.P. and Mueller, R. and Birol, I. and Lehman, A.
DOI: 10.1159/000479463
2017

Incidental finding of paternal UPD15 in a child with a deletion of 11q21-q22.3, presenting with developmental delay, coloboma and characteristic dysmorphic features
Clinical Dysmorphology
Tucker, T. and Steinraths, M. and Oh, T. and Nelson, T.N. and Van Allen, M.I. and Brown, L. and Schlade-Bartusiak, K.
DOI: 10.1097/MCD.0000000000000108
2016

A cryptic familial rearrangement of 11p15.5, involving both imprinting centers, in a family with a history of short stature
American Journal of Medical Genetics, Part A
Brown, L.A. and Rupps, R. and Pe{\~n}aherrera, M.S. and Robinson, W.P. and Patel, M.S. and Eydoux, P. and Boerkoel, C.F.
DOI: 10.1002/ajmg.a.36490
2014

Molecular characterization of a 4 409 480 bp deletion of the human X chromosome in a patient with haemophilia B
Haemophilia
Hewitt, J. and Chou, E.M.H. and Brown, L.A. and Smith, V.C. and Yong, S.-L. and Wadsworth, L.D. and Wu, J.K. and MacGillivray, R.T.A.
DOI: 10.1111/hae.12395
2014

Impact of drought on vector-borne diseases - how does one manage the risk?
Public Health
Brown, L. and Medlock, J. and Murray, V.
DOI: 10.1016/j.puhe.2013.09.006
2014

Use of a care bundle in the emergency department for acute exacerbations of chronic obstructive pulmonary disease: A feasibility study
International Journal of COPD
McCarthy, C. and Brennan, J.R. and Brown, L. and Donaghy, D. and Jones, P. and Whelan, R. and McCormack, N. and Callanan, I. and Ryan, J. and McDonnell, T.J.
DOI: 10.2147/COPD.S52883
2013

A co-occurrence of osteogenesis imperfecta type VI and cystinosis
American Journal of Medical Genetics, Part A
Tucker, T. and Nelson, T. and Sirrs, S. and Roughley, P. and Glorieux, F.H. and Moffatt, P. and Schlade-Bartusiak, K. and Brown, L. and Rauch, F.
DOI: 10.1002/ajmg.a.35319
2012

Uniparental disomy: Can SNP array data be used for diagnosis?
Genetics in Medicine
Tucker, T. and Schlade-Bartusiak, K. and Eydoux, P. and Nelson, T.N. and Brown, L.
DOI: 10.1038/gim.2012.35
2012

BPES with atypical premature ovarian insufficiency, and evidence of mitotic recombination, in a woman with trisomy X and a translocation t(3;11)(q22.3;q14.1)
American Journal of Medical Genetics, Part A
Schlade-Bartusiak, K. and Brown, L. and Lomax, B. and Bruy{\`e}re, H. and Gillan, T. and Hamilton, S. and McGillivray, B. and Eydoux, P.
DOI: 10.1002/ajmg.a.35516
2012

Overwhelming support among urban Irish COPD patients for lung cancer screening by low-dose CT scan
Lung
Pallin, M. and Walsh, S. and O{'}Driscoll, M.F. and Murray, C. and Cahalane, A. and Brown, L. and Carter, M. and Mitchell, P. and McDonnell, T.J. and Butler, M.W.
DOI: 10.1007/s00408-012-9421-9
2012

Co-amplification of CCND1 and EMSY is associated with an adverse outcome in ER-positive tamoxifen-treated breast cancers
Breast Cancer Research and Treatment
Brown, L.A. and Johnson, K. and Leung, S. and Bismar, T.A. and Ben{\'i}tez, J. and Foulkes, W.D. and Huntsman, D.G.
DOI: 10.1007/s10549-009-0479-x
2010

Identification of sister chromatids by DNA template strand sequences
Nature
Falconer, E. and Chavez, E.A. and Henderson, A. and Poon, S.S.S. and McKinney, S. and Brown, L. and Huntsman, D.G. and Lansdorp, P.M.
DOI: 10.1038/nature08644
2010

ESR1 gene amplification in breast cancer: A common phenomenon? [1]
Nature Genetics
Brown, L.A. and Hoog, J. and Chin, S.-F. and Tao, Y. and Zayed, A.A. and Chin, K. and Teschendorff, A.E. and Quackenbush, J.F. and Marioni, J.C. and Leung, S. and Perou, C.M. and Neilsen, T.O. and Ellis, M. and Gray, J.W. and Bernard, P.S. and Huntsman, D.G. and Caldas, C.
DOI: 10.1038/ng0708-806
2008

Molecular determination of the breakpoints of a 161 556 bp deletion at chromosome 13q34 that presented as severe factor VII deficiency in a neonate [7]
British Journal of Haematology
Hewitt, J. and Craven, S.J. and Brown, L.A. and Bleackley, M.R. and Ballard, J.N.M. and Smith, V.C. and Ofosu, F.A. and Huntsman, D.G. and Wadsworth, L.D. and Wu, J.K. and MacGillivray, R.T.A.
DOI: 10.1111/j.1365-2141.2007.06957.x
2008

Distribution and significance of caveolin 2 expression in normal breast and invasive breast cancer: An immunofluorescence and immunohistochemical analysis
Breast Cancer Research and Treatment
Savage, K. and Leung, S. and Todd, S.K. and Brown, L.A. and Jones, R.L. and Robertson, D. and James, M. and Parry, S. and Rodrigues Pinilla, S.M. and Huntsman, D. and Reis-Filho, J.S.
DOI: 10.1007/s10549-007-9718-1
2008

Amplification of 11q13 in ovarian carcinoma
Genes Chromosomes and Cancer
Brown, L.A. and Kalloger, S.E. and Miller, M.A. and Shih, L.-M. and McKinney, S.E. and Santos, J.L. and Swenerton, K. and Spellman, P.T. and Gray, J. and Gilks, C.B. and Huntsman, D.G.
DOI: 10.1002/gcc.20549
2008

Correlates of putting condoms on after sex has begun and of removing them before sex ends: A study of men attending an urban public STD clinic
American Journal of Men's Health
Yarber, W.L. and Crosby, R.A. and Graham, C.A. and Sanders, S.A. and Arno, J. and Hartzell, R.M. and McBride, K. and Milhausen, R. and Brown, L. and Legocki, L.J. and Payne, M. and Rothring, A.
DOI: 10.1177/1557988307301276
2007

Fluorescent in situ hybridization on tissue microarrays: Challenges and solutions
Journal of Molecular Histology
Brown, L.A. and Huntsman, D.
DOI: 10.1007/s10735-006-9069-y
2007

Amplification of EMSY, a novel oncogene on 11q13, in high grade ovarian surface epithelial carcinomas
Gynecologic Oncology
Brown, L.A. and Irving, J. and Parker, R. and Kim, H. and Press, J.Z. and Longacre, T.A. and Chia, S. and Magliocco, A. and Makretsov, N. and Gilks, B. and Pollack, J. and Huntsman, D.
DOI: 10.1016/j.ygyno.2005.08.026
2006

Genomic instability of human mammary epithelial cells overexpressing a truncated form of EMSY
Journal of the National Cancer Institute
Raouf, A. and Brown, L. and Vrcelj, N. and To, K. and Kwok, W. and Huntsman, D.H. and Eaves, C.J.E.
DOI: 10.1093/jnci/dji254
2005

NRG1 gene rearrangements in clinical breast cancer: Identification of an adjacent novel amplicon associated with poor prognosis
Oncogene
Prentice, L.M. and Shadeo, A. and Lestou, V.S. and Miller, M.A. and DeLeeuw, R.J. and Makretsov, N. and Turbin, D. and Brown, L.A. and Macpherson, N. and Yorida, E. and Cheang, M.C.U. and Bentley, J. and Chia, S. and Nielsen, T.O. and Gilks, C.B. and Lam, W. and Huntsman, D.G.
DOI: 10.1038/sj.onc.1208892
2005

Assessment of Her-1, Her-2, and Her-3 expression and Her-2 amplification in advanced stage ovarian carcinoma
International Journal of Gynecological Pathology
Lee, C.-H. and Huntsman, D.G. and Cheang, M.C.U. and Parker, R.L. and Brown, L. and Hoskins, P. and Miller, D. and Gilks, C.B.
DOI: 10.1097/01.pgp.0000152026.39268.57
2005

EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer
Cell
Hughes-Davies, L. and Huntsman, D. and Ruas, M. and Fuks, F. and Bye, J. and Chin, S.-F. and Milner, J. and Brown, L.A. and Hsu, F. and Gilks, B. and Nielsen, T. and Schulzer, M. and Chia, S. and Ragaz, J. and Cahn, A. and Linger, L. and Ozdag, H. and Cattaneo, E. and Jordanova, E.S. and Schuuring, E. and Yu, D.S. and Venkitaraman, A. and Ponder, B. and Doherty, A. and Aparicio, S. and Bentley, D. and Theillet, C. and Ponting, C.P. and Caldas, C. and Kouzarides, T.
DOI: 10.1016/S0092-8674(03)00930-9
2003

Mechanisms of monozygotic (MZ) twinning: A possible role for the cell adhesion molecule, E-cadherin
American Journal of Medical Genetics
Bamforth, F. and Brown, L. and Senz, J. and Huntsman, D.
DOI: 10.1002/ajmg.a.20076
2003

CDH1 c-160a promotor polymorphism is not associated with risk of stomach cancer
International Journal of Cancer
Pharoah, P.D.P. and Oliveira, C. and Machado, J.C. and Keller, G. and Vogelsang, H. and Laux, H. and Becker, K.-F. and Hahn, H. and Paproski, S.M. and Brown, L.A. and Caldas, C. and Huntsman, D.
DOI: 10.1002/ijc.10590
2002

Effect of manually assisted cough and mechanical insufflation on cough flow of normal subjects, patients with chronic obstructive pulmonary disease (COPD), and patients with respiratory muscle weakness
Thorax
Sivasothy, P. and Brown, L. and Smith, I.E. and Shneerson, J.M.
DOI: 10.1136/thorax.56.6.438
2001

Fabrication of a customized cuirass for patients with severe thoracic asymmetry.
The American review of respiratory disease
Shneerson, J.M. and Brown, L.
DOI: 10.1164/ajrccm/138.2.488b
1988

Artificial ventilation by external negative pressure. A method for manufacturing cuirass shells
Physiotherapy
Brown, L. and Kinnear, W. and Sergeant, K.A. and Shneerson, J.
1985

Research

Current projects
Acute leukemia has been well characterized genetically, largely due to the successful implementation of cytogenetic techniques to identify large chromosomal abnormalities, the detection of which has proven important in terms of diagnosis, prognosis and treatment. There has been an effort to use high resolution genomic profiling to identify novel genetic alterations that contribute to leukemogenesis.

Several microarray-based techniques for the genome-wide assessment of DNA copy number alterations (CNA) are now routinely used in the study of cancer genetics. Currently, the Cytogenetics Laboratory at C&W uses numerous cyotogenetic techniques, including karyotype, fluorescent in-situ hybridization, and more recently microarray to provide a comprehensive genomic analysis of pediatric acute leukemia. The power of microarray is that it can identify small CNA's and well as regions of copy number-neutral loss of heterozygosity (CN-LOH).

Currently, all leukemia’s are evaluated in the Cytogenetics laboratory and CMA is performed. Established clinical thresholds are used for identifying CNAs. The aim of the current research project is to furhter explore the existing data looking at much smaller CNAs (outside of the clinical thresholds) and assess CN-LOH. The use of SNP-arrays to identify somatically altered regions of the genome is anticipated to lead to the discovery of clinically relevant genes involved in leukemogenesis.

Grants

BCCH Telethon Award 2012, Genome wide assessment of genetic alterations in pediatric acute lymphoblastic leukemia

BCCH Telethon Award 2010, Discovery of novel candidate genes involved in facial clefting

A pilot project

Honours & Awards

CCMG Fellowship Salary Award, UBC, 2008

Travel Fellowship for the Helene Harris Memorial Trust 11th International Forum on Ovarian Cancer, Lake Como, Italy, 2007

Linda Stevens Memorial Fund (CCMG), 2008