Hereditary Colon Cancer Genetic Testing Panel Overview | ColoNext® | Ambry Genetics

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06/30/23

For more information about this genetic test, visit: https://www.ambrygen.com/clini....cian/genetic-testing

Patients with a suspicious personal or family history of colorectal cancer or polyps benefit from early detection and cancer prevention. Identify patients with an increased risk by using ColoNext, a 17-gene panel designed to provide more precise data to help guide personalized medical management recommendations such as earlier or more frequent colonoscopies.

Test Description
ColoNext analyzes 17 genes (listed above). 15 genes (excluding EPCAM and GREM1) are evaluated by next generation sequencing (NGS) or Sanger sequencing of all coding domains, and well into the flanking 5’ and 3’ ends of all the introns and untranslated regions. In addition, sequencing of the promoter region is performed for the following genes: PTEN (c.-1300 to c.-745), MLH1 (c.-337 to c.-194), and MSH2 (c.-318 to c.-65). For POLD1 and POLE, missense variants located outside of the exonuclease domains (codons 311-541 and 269-485, respectively) are not routinely reported. The inversion of coding exons 1-7 of the MSH2 gene is detected by NGS and confirmed by PCR and agarose gel electrophoresis. 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. Additional Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Reportable small insertions and deletions, potentially homozygous variants, variants in regions complicated by pseudogene interference, and single nucleotide variant calls not satisfying 100x depth of coverage and 40% het ratio thresholds are verified by Sanger sequencing.1 Gross deletion/duplication analysis is performed for the covered exons and untranslated regions of all 17 genes using read-depth from NGS data with confirmatory multiplex ligation-dependent probe amplification (MLPA) and/or targeted chromosomal microarray. For GREM1, only the status of the 40kb 5’ UTR gross duplication is analyzed and reported. For APC, all promoter 1B gross deletions as well as single nucleotide substitutions within the promoter 1B YY1 binding motif are analyzed and reported. If a deletion is detected in exons 13, 14, or 15 of PMS2, double stranded sequencing of the appropriate exon(s) of the pseudogene, PMS2CL, will be performed to determine if the deletion is located in the PMS2 gene or pseudogene.