CancerNext®

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CancerNext^® is a comprehensive 36-gene panel that identifies inherited risks for at least 8 types of cancers, giving you more information for treatment and management decisions. Why Is This Important?

• Option to modify frequency and initial age of mammogram/breast MRI, colonoscopy, prostate cancer screening, or other screening as appropriate
• Consideration of prophylactic mastectomy, colectomy, or other risk-reducing measures, as appropriate
• Option to tailor treatment and/or determine eligibility for clinical trials
• Identify at-risk family members

When To Consider Testing?

• Multiple primary tumours in one person that are suspicious for a combination of hereditary breast, ovarian, colorectal, uterine cancers and/or melanoma
• 3 or more close family members with cancers, such as breast, ovarian, colorectal, and uterine, that are suspicious for hereditary cancer
• Previous genetic testing was uninformative (negative or variant of uncertain significance) for a patient with a personal and/or family history suspicious for hereditary cancer

Test Method CancerNext^® analyses 36 genes. These genes (excludingEPCAMandGREM1) 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. For POLD1 and POLE, only missense and in-frame indel variants in the exonuclease domains (codons 311-541 and 269-485, respectively) are routinely reported. For HOXB13, only variants impacting codon 84 are routinely reported. For RECQL, only missense variants in the helicase and RCQ domains (codons 63-592) and exonic truncating variants are routinely reported. The MSH3 polyalanine repeat region is excluded from analysis. The inversion of coding exons 1-7 of theMSH2gene and theBRCA2Portuguese founder mutation, c.156_157insAlu (also known as 384insAlu) are 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. 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 is performed for the covered exons and untranslated regions of all sequenced genes (excluding AXIN2, HOXB13, MSH3, POLD1, POLE) using read-depth from NGS data with confirmatory multiplex ligation-dependent probe amplification (MLPA) and/or targeted chromosomal microarray. ForGREM1, only the status of the 40kb 5’ UTR gross duplication is analysed and reported. For EPCAM, only gross deletions encompassing the 3’ end of the gene are reported. For NTHL1, only full-gene gross deletions and duplications are detected. ForAPC,all promoter 1B gross deletions as well as single nucleotide substitutions within the promoter 1B YY1 binding motif (NM_001127511 c.-196_c.-186) are analysed and reported. Gross deletion/duplication analysis of PMS2is performed using MLPA. If a deletion is detected in exons 13, 14, or 15 ofPMS2, double-stranded sequencing of the appropriate exon(s) of the pseudogene, PMS2CL, will be performed to determine if the deletion is located in thePMS2gene or pseudogene. © 2023 Ambry Genetics. All Rights Reserved.