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Evaluation of illumina trusight cardiomyopathy panel testing for detection of diagnostically relevant abnormalities in hypertrophic cardiomyopathy
S104
PATHOLOGY 2017 ABSTRACT SUPPLEMENT
to adulthood. Through simple dietary modification, Psammomys obesus develop obesity that closely resembles the metabolic changes of high calorie consumption in humans.3 Methods: Methyl-CpG binding domain capture and deep sequencing (MBD-seq) were used to examine the hypothalamus of Psammomys obesus offspring exposed to a low-fat diet and standard chow diet during the gestation and lactation period. Results: Offspring exposed to a low-fat parental diet were more obese and had increased circulating insulin and glucose levels. Hypothalamic methylome profiling identified 1,447 genomic regions of differential methylation between low-fat parental diet offspring compared to high-fat parental offspring. Pathway analysis revealed novel changes in DNA methylation of hypothalamic genes associated with neurological function, nutrient sensing, appetite and energy balance, which corresponded to alternations in hypothalamic gene expression in the low-fat parental diet offspring. Conclusion: Subject to parental low-fat diet, we observe DNA methylation changes of genes associated with obesity in offspring. References
Pathology (2017), 49(S1)
option. Automated variant analysis contributes to improved turnaround time, but results must be validated by a multidisciplinary cardiac pathogenicity team. DEVELOPING A QUALITY ASSURANCE PROGRAM ON THE DETECTION OF ANAPLASTIC LYMPHOMA KINASE (ALK) GENE REARRANGEMENT IN NONSMALL CELL LUNG CANCER (NSCLC) Kwang Hong Tay1, Nalishia Pillay1, Sze Chai1, Bruce Bennetts2, Martin Horan1 1 RCPAQAP Molecular Genetics, St Leonards, and 2Children’s Hospital at Westmead, Westmead, NSW, Australia
EVALUATION OF ILLUMINA TRUSIGHT CARDIOMYOPATHY PANEL TESTING FOR DETECTION OF DIAGNOSTICALLY RELEVANT ABNORMALITIES IN HYPERTROPHIC CARDIOMYOPATHY
The Molecular Genetics Discipline at the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) offers quality assurance on a spectrum of molecular genetic analyses involved with human disease. Quality assurance can be offered on any human genetic test, but programs can only be developed and offered if there is a sufficient demand for the molecular test. As such, quality assurance on the ALK translocation in NSCLC was offered in 2015 as a pilot module owing to increased demand. Participation in the ALK-specific module has since grown over the past two years and now encompasses 15 laboratories. This report is a representation of the 2015–2016 survey pilot data for the ALK gene rearrangement module. The module was designed to assess inter-laboratory performance to detect an ALK genetic rearrangement from a patient-derived formalin fixed paraffin embedded (FFPE) tumour tissue sample and to provide interpretative comments on their findings. RCPAQAP-specific survey reports were generated and reflect the level of participant concordance. Included in each participant survey report are the specific methods performed for analysis, a list of peer-reviewed published articles used for interpretative comments, and importantly, those areas that need to be addressed for improved of performance.
Simon Cliffe1, Richard Bagnall2, Jodie Ingles2, Matthew Bainbridge3, Melody Caramins1,4, Chris Semsarian2 1 Specialist Diagnostic Services (SDS Pathology, Genomic Diagnostics), 2Centenary Institute, 3Codified Genomics, and 4 University of New South Wales, Australia
MITOCHONDRIAL GENOME CONTENT IS DECREASED IN PROSTATE CANCER OVERALL, BUT INCREASED IN HIGH GRADE CANCER
1. Keating ST, El-Osta A. Epigenetics and metabolism. Circ Res 2015; 116: 715–36. 2. Desai M, Jellyman JK, Ross MG. Epigenomics, gestational programming and risk of metabolic syndrome. Int J Obes (Lond) 2015; 39: 633–41. 3. Walder KR, Fahey RP, Morton GJ, et al. Characterization of obesity phenotypes in Psammomys obesus (Israeli sand rats). Int J Exp Diabetes Res 2000; 1: 177–84.
Introduction: Hypertrophic cardiomyopathy (HCM) is the most common familial heart disease, with a prevalence of up to 1 in 200. Screening of 5–11 HCM genes yields a diagnostic rate of 20–63% in unselected patients. We assessed the diagnostic yield, clinical utility and performance of the TruSight Cardiomyopathy gene panel (TCGP) in conjunction with an automated variant analysis pipeline in Australian patients with HCM. Method: 117 patients referred from a specialty genetics cardiology setting with a diagnosis of HCM were sequenced on an Illumina MiSeq, using the TCGP. Data were analysed with the Codified Genomics pipeline, and pathogenic variants were validated by Sanger sequencing. Results: Between 80–150 SNVs and 2–6 indels were identified in each sample, of which 98 were deemed candidate mutations by the Codified Genomics pipeline. Manual review of candidate mutations indicated that 76% were pathogenic or likely pathogenic. Discussion: Clinical genetic testing using the TCGP yielded a potential diagnosis in 49.5% of patients and identified multiple variants in 4 patients. The time from diagnosis to identification of a causative variant is substantially reduced compared to Sanger sequencing, and makes panel-based testing a very attractive
Anton M. F. Kalsbeek1,2, Eva F. K. Chan1,2, Judith Grogan3,4,5, Desiree C. Petersen1,2, Weerachai Jaratlerdsiri1, Ruta Gupta3,4,5, Ruth J. Lyons1, Anne-Maree Haynes5, Lisa G. Horvath5,6, James G. Kench3,4,5, Phillip D. Stricker7, Vanessa M. Hayes1,2,4 1 Laboratory for Human Comparative and Prostate Cancer Genomics, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, 2School of Medical Sciences, University of New South Wales, Randwick, 3 Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, 4Central Clinical School, Sydney Medical School, University of Sydney, Camperdown, 5Cancer Research Division, The Kinghorn Cancer Centre/Garvan Institute of Medical Research, Darlinghurst, 6Chris O’Brien Lifehouse, Camperdown, and 7 Department of Urology, St. Vincent’s Hospital, Darlinghurst, NSW, Australia Prostate cancer was recently found to have a reduced mitochondrial genome (mtDNA) content. We aim to discover the correlation with mtDNA content, tumour pathology and clinical outcome. Fresh prostate cancer biopsies from 115 patients were
PATHOLOGY 2017 ABSTRACT SUPPLEMENT
to adulthood. Through simple dietary modification, Psammomys obesus develop obesity that closely resembles the metabolic changes of high calorie consumption in humans.3 Methods: Methyl-CpG binding domain capture and deep sequencing (MBD-seq) were used to examine the hypothalamus of Psammomys obesus offspring exposed to a low-fat diet and standard chow diet during the gestation and lactation period. Results: Offspring exposed to a low-fat parental diet were more obese and had increased circulating insulin and glucose levels. Hypothalamic methylome profiling identified 1,447 genomic regions of differential methylation between low-fat parental diet offspring compared to high-fat parental offspring. Pathway analysis revealed novel changes in DNA methylation of hypothalamic genes associated with neurological function, nutrient sensing, appetite and energy balance, which corresponded to alternations in hypothalamic gene expression in the low-fat parental diet offspring. Conclusion: Subject to parental low-fat diet, we observe DNA methylation changes of genes associated with obesity in offspring. References
Pathology (2017), 49(S1)
option. Automated variant analysis contributes to improved turnaround time, but results must be validated by a multidisciplinary cardiac pathogenicity team. DEVELOPING A QUALITY ASSURANCE PROGRAM ON THE DETECTION OF ANAPLASTIC LYMPHOMA KINASE (ALK) GENE REARRANGEMENT IN NONSMALL CELL LUNG CANCER (NSCLC) Kwang Hong Tay1, Nalishia Pillay1, Sze Chai1, Bruce Bennetts2, Martin Horan1 1 RCPAQAP Molecular Genetics, St Leonards, and 2Children’s Hospital at Westmead, Westmead, NSW, Australia
EVALUATION OF ILLUMINA TRUSIGHT CARDIOMYOPATHY PANEL TESTING FOR DETECTION OF DIAGNOSTICALLY RELEVANT ABNORMALITIES IN HYPERTROPHIC CARDIOMYOPATHY
The Molecular Genetics Discipline at the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) offers quality assurance on a spectrum of molecular genetic analyses involved with human disease. Quality assurance can be offered on any human genetic test, but programs can only be developed and offered if there is a sufficient demand for the molecular test. As such, quality assurance on the ALK translocation in NSCLC was offered in 2015 as a pilot module owing to increased demand. Participation in the ALK-specific module has since grown over the past two years and now encompasses 15 laboratories. This report is a representation of the 2015–2016 survey pilot data for the ALK gene rearrangement module. The module was designed to assess inter-laboratory performance to detect an ALK genetic rearrangement from a patient-derived formalin fixed paraffin embedded (FFPE) tumour tissue sample and to provide interpretative comments on their findings. RCPAQAP-specific survey reports were generated and reflect the level of participant concordance. Included in each participant survey report are the specific methods performed for analysis, a list of peer-reviewed published articles used for interpretative comments, and importantly, those areas that need to be addressed for improved of performance.
Simon Cliffe1, Richard Bagnall2, Jodie Ingles2, Matthew Bainbridge3, Melody Caramins1,4, Chris Semsarian2 1 Specialist Diagnostic Services (SDS Pathology, Genomic Diagnostics), 2Centenary Institute, 3Codified Genomics, and 4 University of New South Wales, Australia
MITOCHONDRIAL GENOME CONTENT IS DECREASED IN PROSTATE CANCER OVERALL, BUT INCREASED IN HIGH GRADE CANCER
1. Keating ST, El-Osta A. Epigenetics and metabolism. Circ Res 2015; 116: 715–36. 2. Desai M, Jellyman JK, Ross MG. Epigenomics, gestational programming and risk of metabolic syndrome. Int J Obes (Lond) 2015; 39: 633–41. 3. Walder KR, Fahey RP, Morton GJ, et al. Characterization of obesity phenotypes in Psammomys obesus (Israeli sand rats). Int J Exp Diabetes Res 2000; 1: 177–84.
Introduction: Hypertrophic cardiomyopathy (HCM) is the most common familial heart disease, with a prevalence of up to 1 in 200. Screening of 5–11 HCM genes yields a diagnostic rate of 20–63% in unselected patients. We assessed the diagnostic yield, clinical utility and performance of the TruSight Cardiomyopathy gene panel (TCGP) in conjunction with an automated variant analysis pipeline in Australian patients with HCM. Method: 117 patients referred from a specialty genetics cardiology setting with a diagnosis of HCM were sequenced on an Illumina MiSeq, using the TCGP. Data were analysed with the Codified Genomics pipeline, and pathogenic variants were validated by Sanger sequencing. Results: Between 80–150 SNVs and 2–6 indels were identified in each sample, of which 98 were deemed candidate mutations by the Codified Genomics pipeline. Manual review of candidate mutations indicated that 76% were pathogenic or likely pathogenic. Discussion: Clinical genetic testing using the TCGP yielded a potential diagnosis in 49.5% of patients and identified multiple variants in 4 patients. The time from diagnosis to identification of a causative variant is substantially reduced compared to Sanger sequencing, and makes panel-based testing a very attractive
Anton M. F. Kalsbeek1,2, Eva F. K. Chan1,2, Judith Grogan3,4,5, Desiree C. Petersen1,2, Weerachai Jaratlerdsiri1, Ruta Gupta3,4,5, Ruth J. Lyons1, Anne-Maree Haynes5, Lisa G. Horvath5,6, James G. Kench3,4,5, Phillip D. Stricker7, Vanessa M. Hayes1,2,4 1 Laboratory for Human Comparative and Prostate Cancer Genomics, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, 2School of Medical Sciences, University of New South Wales, Randwick, 3 Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, 4Central Clinical School, Sydney Medical School, University of Sydney, Camperdown, 5Cancer Research Division, The Kinghorn Cancer Centre/Garvan Institute of Medical Research, Darlinghurst, 6Chris O’Brien Lifehouse, Camperdown, and 7 Department of Urology, St. Vincent’s Hospital, Darlinghurst, NSW, Australia Prostate cancer was recently found to have a reduced mitochondrial genome (mtDNA) content. We aim to discover the correlation with mtDNA content, tumour pathology and clinical outcome. Fresh prostate cancer biopsies from 115 patients were