Publications (12)260.02 Total impact
-
Article: Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers.
[show abstract] [hide abstract]
ABSTRACT: Germline truncating mutations in DICER1, an endoribonuclease in the RNase III family that is essential for processing microRNAs, have been observed in families with the pleuropulmonary blastoma-family tumor and dysplasia syndrome. Mutation carriers are at risk for nonepithelial ovarian tumors, notably sex cord-stromal tumors. We sequenced the whole transcriptomes or exomes of 14 nonepithelial ovarian tumors and noted closely clustered mutations in the region of DICER1 encoding the RNase IIIb domain of DICER1 in four samples. We then sequenced this region of DICER1 in additional ovarian tumors and in certain other tumors and queried the effect of the mutations on the enzymatic activity of DICER1 using in vitro RNA cleavage assays. DICER1 mutations in the RNase IIIb domain were found in 30 of 102 nonepithelial ovarian tumors (29%), predominantly in Sertoli-Leydig cell tumors (26 of 43, or 60%), including 4 tumors with additional germline DICER1 mutations. These mutations were restricted to codons encoding metal-binding sites within the RNase IIIb catalytic centers, which are critical for microRNA interaction and cleavage, and were somatic in all 16 samples in which germline DNA was available for testing. We also detected mutations in 1 of 14 nonseminomatous testicular germ-cell tumors, in 2 of 5 embryonal rhabdomyosarcomas, and in 1 of 266 epithelial ovarian and endometrial carcinomas. The mutant DICER1 proteins had reduced RNase IIIb activity but retained RNase IIIa activity. Somatic missense mutations affecting the RNase IIIb domain of DICER1 are common in nonepithelial ovarian tumors. These mutations do not obliterate DICER1 function but alter it in specific cell types, a novel mechanism through which perturbation of microRNA processing may be oncogenic. (Funded by the Terry Fox Research Institute and others.).New England Journal of Medicine 12/2011; 366(3):234-42. · 53.30 Impact Factor -
Article: Using next-generation sequencing for the diagnosis of rare disorders: a family with retinitis pigmentosa and skeletal abnormalities.
[show abstract] [hide abstract]
ABSTRACT: Linkage analysis with subsequent candidate gene sequencing is typically used to diagnose novel inherited syndromes. It is now possible to expedite diagnosis through the sequencing of all coding regions of the genome (the exome) or full genomes. We sequenced the exomes of four members of a family presenting with spondylo-epiphyseal dysplasia and retinitis pigmentosa and identified a six-base-pair (6-bp) deletion in GNPTG, the gene implicated in mucolipidosis type IIIγ. The diagnosis was confirmed by biochemical studies and both broadens the mucolipidosis type III phenotype and demonstrates the clinical utility of next-generation sequencing to diagnose rare genetic diseases.The Journal of Pathology 09/2011; 225(1):12-8. · 6.32 Impact Factor -
Article: Subtype-specific mutation of PPP2R1A in endometrial and ovarian carcinomas.
[show abstract] [hide abstract]
ABSTRACT: PPP2R1A mutations have recently been described in 3/42 (7%) of clear cell carcinomas of the ovary. PPP2R1A encodes the α-isoform of the scaffolding subunit of the serine/threonine protein phosphatase 2A (PP2A) holoenzyme. This putative tumour suppressor complex is involved in growth and survival pathways. Through targeted sequencing of PPP2R1A, we identified somatic missense mutations in 40.8% (20/49) of high-grade serous endometrial tumours, and 5.0% (3/60) of endometrial endometrioid carcinomas. Mutations were also identified in ovarian tumours at lower frequencies: 12.2% (5/41) of endometrioid and 4.1% (2/49) of clear cell carcinomas. No mutations were found in 50 high-grade and 12 low-grade serous carcinomas. Amino acid residues affected by these mutations are highly conserved across species and are involved in direct interactions with regulatory B-subunits of the PP2A holoenzyme. PPP2R1A mutations in endometrial high-grade serous carcinomas are a frequent and potentially targetable feature of this disease. The finding of frequent PPP2R1A mutations in high-grade serous carcinoma of the endometrium but not in high-grade serous carcinoma of the ovary provides clear genetic evidence that these are distinct diseases.The Journal of Pathology 01/2011; 223(5):567-73. · 6.32 Impact Factor -
Article: ARID1A mutations in endometriosis-associated ovarian carcinomas.
[show abstract] [hide abstract]
ABSTRACT: Ovarian clear-cell and endometrioid carcinomas may arise from endometriosis, but the molecular events involved in this transformation have not been described. We sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI–SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas. ARID1A mutations were seen in 55 of 119 ovarian clear-cell carcinomas (46%), 10 of 33 endometrioid carcinomas (30%), and none of the 76 high-grade serous ovarian carcinomas. Seventeen carcinomas had two somatic mutations each. Loss of the BAF250a protein correlated strongly with the ovarian clear-cell carcinoma and endometrioid carcinoma subtypes and the presence of ARID1A mutations. In two patients, ARID1A mutations and loss of BAF250a expression were evident in the tumor and contiguous atypical endometriosis but not in distant endometriotic lesions. These data implicate ARID1A as a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas. Since ARID1A mutation and loss of BAF250a can be seen in the preneoplastic lesions, we speculate that this is an early event in the transformation of endometriosis into cancer. (Funded by the British Columbia Cancer Foundation and the Vancouver General Hospital–University of British Columbia Hospital Foundation.).New England Journal of Medicine 10/2010; 363(16):1532-43. · 53.30 Impact Factor -
Article: Mutation of FOXL2 in granulosa-cell tumors of the ovary.
[show abstract] [hide abstract]
ABSTRACT: Granulosa-cell tumors (GCTs) are the most common type of malignant ovarian sex cord-stromal tumor (SCST). The pathogenesis of these tumors is unknown. Moreover, their histopathological diagnosis can be challenging, and there is no curative treatment beyond surgery. We analyzed four adult-type GCTs using whole-transcriptome paired-end RNA sequencing. We identified putative GCT-specific mutations that were present in at least three of these samples but were absent from the transcriptomes of 11 epithelial ovarian tumors, published human genomes, and databases of single-nucleotide polymorphisms. We confirmed these variants by direct sequencing of complementary DNA and genomic DNA. We then analyzed additional tumors and matched normal genomic DNA, using a combination of direct sequencing, analyses of restriction-fragment-length polymorphisms, and TaqMan assays. All four index GCTs had a missense point mutation, 402C-->G (C134W), in FOXL2, a gene encoding a transcription factor known to be critical for granulosa-cell development. The FOXL2 mutation was present in 86 of 89 additional adult-type GCTs (97%), in 3 of 14 thecomas (21%), and in 1 of 10 juvenile-type GCTs (10%). The mutation was absent in 49 SCSTs of other types and in 329 unrelated ovarian or breast tumors. Whole-transcriptome sequencing of four GCTs identified a single, recurrent somatic mutation (402C-->G) in FOXL2 that was present in almost all morphologically identified adult-type GCTs. Mutant FOXL2 is a potential driver in the pathogenesis of adult-type GCTs.New England Journal of Medicine 06/2009; 360(26):2719-29. · 53.30 Impact Factor -
Article: Ovarian carcinoma subtypes are different diseases: implications for biomarker studies.
[show abstract] [hide abstract]
ABSTRACT: Although it has long been appreciated that ovarian carcinoma subtypes (serous, clear cell, endometrioid, and mucinous) are associated with different natural histories, most ovarian carcinoma biomarker studies and current treatment protocols for women with this disease are not subtype specific. With the emergence of high-throughput molecular techniques, distinct pathogenetic pathways have been identified in these subtypes. We examined variation in biomarker expression rates between subtypes, and how this influences correlations between biomarker expression and stage at diagnosis or prognosis. In this retrospective study we assessed the protein expression of 21 candidate tissue-based biomarkers (CA125, CRABP-II, EpCam, ER, F-Spondin, HE4, IGF2, K-Cadherin, Ki-67, KISS1, Matriptase, Mesothelin, MIF, MMP7, p21, p53, PAX8, PR, SLPI, TROP2, WT1) in a population-based cohort of 500 ovarian carcinomas that was collected over the period from 1984 to 2000. The expression of 20 of the 21 biomarkers differs significantly between subtypes, but does not vary across stage within each subtype. Survival analyses show that nine of the 21 biomarkers are prognostic indicators in the entire cohort but when analyzed by subtype only three remain prognostic indicators in the high-grade serous and none in the clear cell subtype. For example, tumor proliferation, as assessed by Ki-67 staining, varies markedly between different subtypes and is an unfavourable prognostic marker in the entire cohort (risk ratio [RR] 1.7, 95% confidence interval [CI] 1.2%-2.4%) but is not of prognostic significance within any subtype. Prognostic associations can even show an inverse correlation within the entire cohort, when compared to a specific subtype. For example, WT1 is more frequently expressed in high-grade serous carcinomas, an aggressive subtype, and is an unfavourable prognostic marker within the entire cohort of ovarian carcinomas (RR 1.7, 95% CI 1.2%-2.3%), but is a favourable prognostic marker within the high-grade serous subtype (RR 0.5, 95% CI 0.3%-0.8%). The association of biomarker expression with survival varies substantially between subtypes, and can easily be overlooked in whole cohort analyses. To avoid this effect, each subtype within a cohort should be analyzed discretely. Ovarian carcinoma subtypes are different diseases, and these differences should be reflected in clinical research study design and ultimately in the management of ovarian carcinoma.PLoS Medicine 01/2009; 5(12):e232. · 16.27 Impact Factor -
Article: Automated quantitative analysis of estrogen receptor expression in breast carcinoma does not differ from expert pathologist scoring: a tissue microarray study of 3,484 cases.
[show abstract] [hide abstract]
ABSTRACT: Estrogen receptor (ER) expression is routinely assessed by immunohistochemistry (IHC) in breast carcinoma. Our study compares visual scoring of ER in invasive breast cancer by histopathologists to quantitation of staining using a fully automated system. A tissue microarray was constructed from 4,049 cases (3,484 included in analysis) of invasive breast carcinoma linked to treatment and outcome information. Slides were scored independently by two pathologists and scores were dichotomised, with ER positivity recognized at a cut-off of >1% positive nuclei. The slides were scanned and analyzed with an Ariol automated system. Using data dichotomised as ER positive or negative, both visual and automated scores were highly consistent: there was excellent concordance between two pathologists (kappa = 0.918 (95%CI: 0.903-0.932)) and between two Ariol machines (kappa = 0.913 (95%CI: 0.897-0.928)). The prognostic significance of ER positivity was similar whether determined by pathologist or automated scoring for both the entire patient cohort and subsets of patients treated with tamoxifen alone or receiving no systemic adjuvant therapy. The optimal cut point for the automated scores using breast cancer disease-specific survival as an endpoint was >0.4% positive nuclei. The concordance between dextran-coated charcoal ER biochemical assay data and automated scores (kappa = 0.728 (95%CI: 0.69-0.75); 0.74 (95%CI: 0.71-0.77)) was similar to the concordance between biochemical assay and pathologist scores (kappa = 0.72 (95%CI: 0.70-0.75; 0.70 (95%CI: 0.67-0.72)). Fully automated quantitation of ER immunostaining yields results that do not differ from human scoring against both biochemical assay and patient outcome gold standards.Breast Cancer Research and Treatment 09/2008; 110(3):417-26. · 4.43 Impact Factor -
Article: Hereditary diffuse gastric cancer: association with lobular breast cancer.
[show abstract] [hide abstract]
ABSTRACT: Hereditary diffuse gastric cancer (HDGC) has been shown to be caused by germline mutations in the gene CDH1 located at 16q22.1, which encodes the cell-cell adhesion molecule, E-cadherin. Not only does loss of expression of E-cadherin account for the morphologic differences between intestinal and diffuse gastric cancer (DGC) variants, but it also appears to lead to distinct cellular features which appear to be common amongst related cancers that have been seen in the syndrome. As in most hereditary cancer syndromes, multiple organ sites may be commonly affected by cancer, in HDGC, lobular carcinoma of the breast (LBC) and possibly other organ sites have been shown to be associated with the familial cancer syndrome. Given the complexity of HDGC, not only with regard to the management of the DGC risk, but also with regard to the risk for other related cancers, such as LBC, a multi-disciplinary approach is needed for the management of individuals with known CDH1 mutations.Familial Cancer 02/2008; 7(1):73-82. · 1.30 Impact Factor -
Article: Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities.
[show abstract] [hide abstract]
ABSTRACT: Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumours were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumours with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.BMC Cancer 02/2008; 8:17. · 3.01 Impact Factor -
Article: Frequency of the TMPRSS2:ERG gene fusion is increased in moderate to poorly differentiated prostate cancers.
[show abstract] [hide abstract]
ABSTRACT: Recent reports indicate that prostate cancers (CaP) frequently over-express the potential oncogenes, ERG or ETV1. Many cases have chromosomal rearrangements leading to the fusion of the 5' end of the androgen-regulated serine protease TMPRSS2 (21q22.2) to the 3' end of either ERG (21q22.3) or ETV1 (7p21.3). The consequence of these rearrangements is aberrant androgen receptor-driven expression of the potential oncogenes, ETV1 or ERG. To determine the frequency of rearrangements involving TMPRSS2, ERG, or ETV1 genes in CaP of varying Gleason grades through fluorescence in situ hybridisation (FISH) on CaP tissue microarrays (TMAs). Two independent assays, a TMPRSS2 break-apart assay and a three-colour gene fusion FISH assay were applied to TMAs. FISH positive cases were confirmed by reverse transcriptase (RT) PCR and DNA sequence analysis. A total of 106/196 (54.1%) cases were analysed by FISH. None of the five benign prostatic hyperplasia cases analysed exhibited these gene rearrangements. TMPRSS2:ERG fusion was found more frequently in moderate to poorly differentiated tumours (35/86, 40.7%) than in well differentiated tumours (1/15, 6.7%, p = 0.017). TMPRSS2:ETV1 gene fusions were not detected in any of the cases tested. TMPRSS2:ERG fusion product was verified by RT-PCR followed by DNA sequencing in 7/7 randomly selected positive cases analysed. This study indicates that TMPRSS2:ERG gene rearrangements in CaP may be used as a diagnostic tool to identify prognostically relevant sub-classifications of these cancers.Journal of clinical pathology 12/2007; 60(11):1238-43. · 2.43 Impact Factor -
Article: Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer.
[show abstract] [hide abstract]
ABSTRACT: Hereditary diffuse gastric cancer is caused by germline mutations in the epithelial cadherin (CDH1) gene and is characterized by an increased risk for diffuse gastric cancer and lobular breast cancer. To determine whether recurring germline CDH1 mutations occurred due to independent mutational events or common ancestry. Thirty-eight families diagnosed clinically with hereditary diffuse gastric cancer were accrued between November 2004 and January 2006 and were analyzed for CDH1 mutations as part of an ongoing study at the British Columbia Cancer Agency. Twenty-six families had at least 2 gastric cancer cases with 1 case of diffuse gastric cancer in a person younger than 50 years; 12 families had either a single case of diffuse gastric cancer diagnosed in a person younger than 35 years or multiple cases of diffuse gastric cancer diagnosed in persons older than 50 years. Classification of family members as carriers or noncarriers of CDH1 mutations. Haplotype analysis to assess recurring mutations for common ancestry was performed on 7 families from this study and 7 previously reported families with the same mutations. Thirteen mutations (6 novel) were identified in 15 of the 38 families (40% detection rate). The 1137G>A splicing mutation and the 1901C>T (A634V) missense/splicing mutation occurred on common haplotypes in 2 families but on different haplotypes in a third family. The 2195G>A (R732Q) missense/splicing mutation occurred in 2 families on different haplotypes. The 2064-2065delTG mutation occurred on a common haplotype in 2 families. Two families from this study plus 2 additional families carrying the novel 2398delC mutation shared a common haplotype, suggesting a founder effect. All 4 families originate from the southeast coast of Newfoundland. Due to concentrations of lobular breast cancer cases, 2 branches of this family had been diagnosed as having hereditary breast cancer and were tested for BRCA mutations. Within these 4 families, the cumulative risk by age 75 years in mutation carriers for clinically detected gastric cancer was 40% (95% confidence interval [CI], 12%-91%) for males and 63% (95% CI, 19%-99%) for females and the risk for breast cancer in female mutation carriers was 52% (95% CI, 29%-94%). Recurrent CDH1 mutations in families with hereditary diffuse gastric cancer are due to both independent mutational events and common ancestry. The presence of a founder mutation from Newfoundland is strongly supported.JAMA The Journal of the American Medical Association 07/2007; 297(21):2360-72. · 30.03 Impact Factor -
Article: Founder and Recurrent CDH1 Mutations in Families With Hereditary Diffuse Gastric Cancer
[show abstract] [hide abstract]
ABSTRACT: Context Hereditary diffuse gastric cancer is caused by germline mutations in the epithelial cadherin (CDH1) gene and is characterized by an increased risk for diffuse gastric cancer and lobular breast cancer.Objective To determine whether recurring germline CDH1 mutations occurred due to independent mutational events or common ancestry.Design, Setting, and Patients Thirty-eight families diagnosed clinically with hereditary diffuse gastric cancer were accrued between November 2004 and January 2006 and were analyzed for CDH1 mutations as part of an ongoing study at the British Columbia Cancer Agency. Twenty-six families had at least 2 gastric cancer cases with 1 case of diffuse gastric cancer in a person younger than 50 years; 12 families had either a single case of diffuse gastric cancer diagnosed in a person younger than 35 years or multiple cases of diffuse gastric cancer diagnosed in persons older than 50 years.Main Outcome Measures Classification of family members as carriers or noncarriers of CDH1 mutations. Haplotype analysis to assess recurring mutations for common ancestry was performed on 7 families from this study and 7 previously reported families with the same mutations.Results Thirteen mutations (6 novel) were identified in 15 of the 38 families (40% detection rate). The 1137G>A splicing mutation and the 1901C>T (A634V) missense/splicing mutation occurred on common haplotypes in 2 families but on different haplotypes in a third family. The 2195G>A (R732Q) missense/splicing mutation occurred in 2 families on different haplotypes. The 2064-2065delTG mutation occurred on a common haplotype in 2 families. Two families from this study plus 2 additional families carrying the novel 2398delC mutation shared a common haplotype, suggesting a founder effect. All 4 families originate from the southeast coast of Newfoundland. Due to concentrations of lobular breast cancer cases, 2 branches of this family had been diagnosed as having hereditary breast cancer and were tested for BRCA mutations. Within these 4 families, the cumulative risk by age 75 years in mutation carriers for clinically detected gastric cancer was 40% (95% confidence interval [CI], 12%-91%) for males and 63% (95% CI, 19%-99%) for females and the risk for breast cancer in female mutation carriers was 52% (95% CI, 29%-94%).Conclusions Recurrent CDH1 mutations in families with hereditary diffuse gastric cancer are due to both independent mutational events and common ancestry. The presence of a founder mutation from Newfoundland is strongly supported.Conclusions Published online June 3, 2007 (doi:10.1001/jama.297.21.2360). Figures in this Article Gastric cancer is the second most common cause of cancer death worldwide.1 Two major histopathological variants of this cancer have been described: an intestinal type and a diffuse type.2 A decline in the overall incidence of gastric cancer can be attributed primarily to a decrease of the intestinal variant of gastric cancer with the diffuse type remaining stable or possibly even increasing.3 The histopathologic appearance of diffuse gastric cancer specimens reveals a pattern of isolated, mucin-filled tumor cells within the wall of the stomach.4 Decreased expression of the epithelial cadherin (CDH1) gene (Online Mendelian Inheritance in Man No. 192090) in cases of diffuse gastric cancer may account for morphological differences between intestinal and diffuse variants. Epithelial cadherin is a transmembrane glycoprotein and plays a major role in epithelial architecture, cell adhesion, and cell invasion. CDH1 was first associated with gastric cancer when somatic mutations were identified in diffuse gastric cancer specimens.5 Since then, germline mutations in CDH1 have been found in families with autosomal dominant susceptibility to hereditary diffuse gastric cancer (HDGC).6- 17 An autosomal dominant cancer susceptibility syndrome, HDGC has an average age of onset of 38 years for clinically detectable diffuse gastric cancer.7,18 Germline mutations in CDH1 are found in 30% to 40% of clinically defined families with HDGC from different ethnic backgrounds, predominantly from low-incident populations.18- 19 The CDH1 mutation spectrum is heterogeneous and includes point mutations, small deletions, and insertions distributed along the entire coding sequence (Table 1).8,20 The identification of CDH1 mutations offers the opportunity of cancer risk-reduction strategies for unaffected at-risk individuals.19,21 Along with a risk of diffuse gastric cancer, there is an excess of lobular breast cancer in families with clinically defined HDGC.8- 9,22- 24 This is not unexpected because loss of CDH1 expression is a cardinal feature of lobular breast cancer and HDGC and both somatic CDH1 mutations and promoter hypermethylation are found frequently in lobular breast cancer but only rarely in infiltrating ductal carcinoma.25- 26 Table Grahic Jump LocationTable 1.CDH1 Mutations Described to Date*+View Large | Save Table | Download Slide (.ppt) | View in Article Context In this study, mutation status was assessed in 38 families with diffuse gastric cancer. The analysis of the 38 families revealed 13 different CDH1 mutations in 15 of these families (40% detection rate). Eight of these mutations were classified as recurring; these included 2 mutations (1 novel, 1 previously reported10) that were found in more than 1 family in this study and 6 additional mutations that had been previously reported.8,11,19,27- 29 This was unexpected because earlier mutation screenings typically reported only novel mutations in single families. Of the more than 50 published pathogenic germline CDH1 mutations, only the 187C>T (R63X) (arginine63stop) truncating mutation,9,30 the 1018A>G (T340A) (threonine340alanine) mutation,12,31 the 1792C>T (R598X) (arginine598stop) truncating mutation,9,13,30 the 1901C>T (A364V) (alanine634valine) mutation,19,27 and the 1003C>T (R335X) (arginine335stop) truncating mutation9,32 have been found in more than 1 family. The latter was found in 3 families due to independent mutational events as demonstrated by haplotype analysis.9 In this study, haplotype analysis was used to determine if 5 of the 8 recurrent mutations within this series occurred due to independent mutational events or founder effects. For 4 of these mutations, at least 2 apparently unrelated families shared the mutation and an associated haplotype at the CDH1 locus. A novel recurrent CDH1 mutation was initially found in 2 families from the southeast region of Newfoundland and subsequently in 2 additional families, both originating from this same region, implying a founder effect. The implications of these data on the genetic testing and counseling of families with HDGC, as well as the novel opportunities created by the discovery of founder mutations, appear herein.JAMA The Journal of the American Medical Association 297(21):2360-2372. · 30.03 Impact Factor
Top co-authors
Top Journals
Institutions
-
2011
-
BC Cancer Agency
Vancouver, British Columbia, Canada
-
-
2007–2011
-
University of British Columbia - Vancouver
- Department of Pathology and Laboratory Medicine
Vancouver, British Columbia, Canada -
Vancouver General Hospital
Vancouver, British Columbia, Canada
-
-
2008
-
Vancouver Coastal Health
Vancouver, British Columbia, Canada
-
