Integrating research in clinical tests.

Providing information to increase understanding of disease.

In addition to using the latest research to improve our test methods, we perform and publish our own research to ensure we are at the leading edge for each disease. We also share all of our mutation information in registered mutation databases for use by other researchers and clinicians. Our referring specialists have access to our banked, anonymized patient samples including detailed clinical information. Our robust, CAP compliant ethics and privacy policies ensure that appropriate consent is in place.

New! – Two Interesting Cases of Molecular Diagnosis For HHT: Low-Level Mosaicism and Abnormal Splicing of ACVRL1

Our team has authored these papers.

RB Papers

Characterisation of retinoblastomas without RB1 mutations: genomic, gene expression, and clinical studies
Rushlow D, Mol BM, Kennett JY, Yee S, Pajovic A, Thériault BL, Prigoda-Lee NL, Spencer C, Dimaras H, Carson TW, Pang R, Massey C, Godbout R, Jiang Z, Zacksenhaus E, Paton K, Moll AC, Houdayer C, Raizis A, Halliday W, Lam WL, Boutros PC, Lohman D, Dorsman JC, Gallie BL.
The Lancet Oncology, Volume 14, Issue 4, Pages 327 – 334, April 2013
Retinoblastoma is the childhood retinal cancer that defined tumour-suppressor genes. Previous work shows that mutation of both alleles of the RB1 retinoblastoma suppressor gene initiates disease. This study characterizes non-familial retinoblastoma tumours with no detectable RB1 mutations.

Dimaras H, Kimani K, Dimba E, Gronsdhl P, White A, Chan H, Gallie BL.
The Lancet, Volume 379, Issue 9824, Pages 1436 – 1446, 14 April 2012
Retinoblastoma is an aggressive eye cancer of infancy and childhood. Survival and the chance of saving vision depend on severity of disease at presentation. Retinoblastoma was the first tumour to draw attention to the genetic aetiology of cancer. Despite good understanding of its aetiology, mortality from retinoblastoma is about 70% in countries of low and middle income, where most affected children live.

Detection of mosaic RB1 mutations in families with retinoblastoma
Rushlow D, Piovesan B, Zhang K, Prigoda-Lee NL, Marchong MN, Clark RD, Gallie BL.
Hum Mutat. 2009 May;30(5):842-51
In some patients an RB1 mutation is mosaic, meaning it is found in only some of their cells. This study found mosaic mutations in 5.5% of bilateral probands (first affected person in family), 3.8% of unilateral probands, and one unaffected parent of a unilateral proband. We discuss the use of highly sensitive methods to detect low level mosaics. Some mosaics might remain undetected using current methods.

Retinoblastoma: the evidence does matter
Prigoda-Lee NL, Rushlow D, Piovesan B, Zhang K, Dimaras H, Pajovic S, Gallie BL.
Cell Oncol. 2009;31(3):249-50.

Patterns of missplicing caused by RB1 gene mutations in patients with retinoblastoma and association with phenotypic expression
Zhang E, Nowak I, Rushlow D, Gallie BL, Lohmann DR.
Human Mutation 2008 Apr 29(4):475-84.
This study analyzed how changes in DNA sequence affected the resulting RNA sequence of the RB1 gene. We found that pathogenic mutations deep in the introns of the gene are rare, and most splicing mutations caused predictable changes in RNA sequence.

Sensitive and efficient detection of RB1 gene mutations enhances care for families with retinoblastoma
Richter S, Vandezande K, Chen N, Zhang K, Sutherland J, Anderson J, Han L, Panton R, Branco P, Gallie BL.
Am J Hum Genet. 2003 Feb;72(2):253-69.
RB1 mutations are usually unique to each family, and can be found throughout the gene. We show in this study that our highly sensitive and efficient methods improve patient outcomes and reduce healthcare costs. We compare hypothetical costs for care of 20 actual RB families with and without molecular testing and show that molecular testing saved an average of $6,591 per family. In addition, 97 at-risk children from 20 representative families avoided 313 surveillance examinations under anesthetic and 852 clinic visits.

Cost comparison of molecular versus conventional screening of relatives at risk for retinoblastoma
Noorani HZ, Khan HN, Gallie BL, Detsky AS.
Am J Hum Genet. 1996 Aug; 59(2):301-7.
An earlier look at the estimated cost savings of molecular screening compared to clinical surveillance.

HHT Papers

Identification of clinically relevant mosaicism in type I hereditary haemorrhagic telangiectasia
Prigoda-Lee NL, Matevski D, Dumitru D, Piovesan B, Rushlow D, Gallie BL.
J Med Genet. 2011 May; 48(5):353-7.
Our lab identified three patients with mosaic mutations in the ENG gene. Each of these patients was the first person in the family recognized as having HHT. We discuss the difficulty in identifying mosaic mutations in HHT patients, and the rarity of mosaicism in HHT. We recommend that in isolated cases of HHT with no mutation found mosaicism should be suspected.

Hereditary haemorrhagic telangiectasia: mutation detection, test sensitivity and novel mutations
Prigoda NL, Savas S, Abdalla SA, Piovesan B, Rushlow D, Vandezande K, Zhang E, Ozcelik H, Gallie BL, Letarte M.
J Med Genet. 2006 Sep;43(9):722-8.
This is a description of our methods for HHT mutation discovery. Our strategy for understanding variants of unknown significance includes several methods, and correctly predicts significance for most published variants.

Our team has contributed to these papers.

Kinesin family member 14: an independent prognostic marker and potential therapeutic target for ovarian cancer.
Thériault BL, Pajovic S, Bernardini MQ, Shaw PA, Gallie BL
Int J Cancer. 2012 Apr 15;130(8):1844-54

Needle core biopsies provide ample material for genomic and proteomic studies of kidney cancer: observations on DNA, RNA, protein extractions and VHL mutation detection
Kurban G, Gallie BL, Leveridge M, Evans A, Rushlow D, Matevski D, Gupta R, Finelli A, Jewett MA.
Pathol Res Pract. 2012 Jan 15;208(1):22-31.

Adult ovarian retinoblastoma genomic profile distinct from prior childhood eye tumor
Soh SY, Dimaras H, Gupta A, Rushlow D, Swallow C, Crump M, Halliday W, Doyle JJ, Babyn P, Héon E, Gallie BL, Chan HS.
Arch Ophthalmol. 2011 Aug;129(8):1101-4.

Using RB1 mutations to assess minimal residual disease in metastatic retinoblastoma
Dimaras H, Rushlow D, Halliday W, Doyle JJ, Babyn P, Abella EM, Williams J, Héon E, Gallie BL, Chan HS.
Transl Res. 2010 Aug;156(2):91-7.

Identification of a mutation in exon 27 of the RB1 gene associated with incomplete penetrance retinoblastoma
Mitter D, Rushlow D, Nowak I, Ansperger-Rescher B, Gallie BL, Lohmann DR.
Fam Cancer. 2009;8(1):55-8.

Loss of RB1 induces non-proliferative retinoma: increasing genomic instability correlates with progression to retinoblastoma
Dimaras H, Khetan V, Halliday W, Orlic M, Prigoda NL, Piovesan B, Marrano P, Corson TW, Eagle RC Jr, Squire JA, Gallie BL.
Hum Mol Genet. 2008 May 15;17(10):1363-72.

One hit, two hits, three hits, more? Genomic changes in the development of retinoblastoma.
Corson TW, Gallie BL
Genes Chromosomes Cancer. 2007 Jul;46(7):617-34.

Human retinoblastoma is not caused by known pRb-inactivating human DNA tumor viruses
Gillison ML, Chen R, Goshu E, Rushlow D, Chen N, Banister C, Creek KE, Gallie BL.
Int J Cancer. 2007 Apr 1;120(7):1482-90.

Profiling genomic copy number changes in retinoblastoma beyond loss of RB1.
Bowles E, Corson TW, Bayani J, Squire JA, Wong N, Lai PB, Gallie BL.
Genes Chromosomes Cancer. 2007 Feb;46(2):118-29

SMAD4 mutations found in unselected HHT patients
Gallione CJ, Richards JA, Letteboer TG, Rushlow D, Prigoda NL, Leedom TP, Ganguly A, Castells A, Ploos van Amstel JK, Westermann CJ, Pyeritz RE, Marchuk DA.
J Med Genet. 2006 Oct;43(10):793-7.

Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease
Abdalla SA, Letarte M.
J Med Genet. 2006 Feb;43(2):97-110.

Cost comparison of genetic and clinical screening in families with hereditary hemorrhagic telangiectasia
Cohen JH, Faughnan ME, Letarte M, Vandezande K, Kennedy SJ, Krahn MD.
Am J Med Genet A. 2005 Aug 30;137(2):153-60.

KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers.
Corson TW, Huang A, Tsao MS, Gallie BL.
Oncogene. 2005 Jul 14;24(30):4741-53.

Novel mutations and polymorphisms in genes causing hereditary hemorrhagic telangiectasia
Abdalla SA, Cymerman U, Rushlow D, Chen N, Stoeber GP, Lemire EG, Letarte M.
Hum Mutat. 2005 Mar;25(3):320-1.

Deletion of RB exons 24 and 25 causes low-penetrance retinoblastoma
Bremner R, Du DC, Connolly-Wilson MJ, Bridge P, Ahmad KF, Mostachfi H,Rushlow D, Dunn JM, Gallie BL.
Am J Hum Genet. 1997 Sep;61(3):556-70.