for all blood relatives of patients who undergo full single gene sequencing, multigene panel testing or exome sequencing at Ambry Genetics and are found to have a pathogenic or likely pathogenic variant. No-cost testing of blood relatives must be completed within 90 days of the original report date. Whenever possible, more closely related relatives should be tested before more distant relatives.
Order NowAccording to the International Gastric Cancer Linkage Consortium (IGCLC), an individual has a clinical diagnosis of HDGC if any of the following criteria are met:1
Ambry’s CDH1 testing is capable of detecting greater than 99.9% of described mutations in the gene, when present (analytic sensitivity).
CDH1 coding exons 1-16 and well into the 5’ and 3’ ends of all the introns and untranslated regions are analyzed by sequencing. Gross deletion/duplication analysis determines gene copy number for coding exons 1-16. Clinically significant intronic findings beyond 5 base pairs are always reported. Intronic variants of unknown or unlikely clinical significance are not reported beyond 5 base pairs from the splice junction. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using a standardized methodology and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by incorporating the gDNA onto a microfluidics chip, along with primer pairs followed by polymerase chain reaction (PCR) and next generation sequencing (NGS). Sanger sequencing is performed for any regions missing, or with insufficient read depth coverage for reliable heterozygous variant detection. Potentially homozygous variants, variants in regions complicated by pseudogene interference, and variant calls not satisfying depth of coverage and variant allele frequency quality thresholds are verified by Sanger sequencing. Gross deletion/duplication analysis of CDH1 using multiplex ligation-dependent probe amplification (MLPA) is also performed.
1. Fitzgerald RC, et al. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet. 2010; 47:436-444.