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Hereditary Cancer Panels White Paper October 2017

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Hereditary Cancer Panels White Paper October 2017 Hereditary Cancer Panels white paper October 2017 Ambry is driven to give healthcare providers the most advanced genetic testing information available so they can determine the best treatment options for their patients. We are the first lab to take part in the largest study ever for hereditary cancer, to reduce the chance of either getting a false positive patient report or one that misses mutations. This is at the heart of why we do what we do: to deliver the most accurate information so all human disease can be understood. April: Data on first March: BreastNext, 2,079 Breast/Ova/Colo September/October: ColoNext, OvaNext, August: PancNext, and CancerNext Cases BrainTumorNext, CancerNext launched PGLNext, RenalNext published (LaDuca et al. July/August: CancerNext- MelanomaNext, launched Genet Med.) Expanded launched ProstateNext launched 2012 2013 2014 2015 2016 2017 March: GYNplus July: CustomNext- June: BRCAplus launched May: BRCAplus Cancer launched June: Paired launched; BRCA1/2 validation and clinical tumor/germline added to BreastNext, implementation paper testing launched OvaNext, CancerNext published (Chong et al., PLoS One) Hereditary Cancer Panel Experience understanding disease better through data sharing and transparency 100 90 80 51.52 70 63.63 60.32 62.30 76.27 69.92 72.02 74.67 71.34 66.67 60 83.45 89.45 84.78 50 1.44 40 1.62 1.39 33.94 30 1.35 1.88 11.04 24.37 26.89 20 14.67 13.37 20.05 16.05 29.63 10.16 16.80 10 22.66 6.52 5.11 11.43 11.17 13.11 8.68 10.61 9.28 15.29 5.44 6.39 6.93 8.70 0 3.70 BRCAplus GYNplus BreastNext OvaNext ColoNext CancerNext CancerNext- RenalNext PancNext ProstateNext BrainTumor- PGLNext MelanomaNext Expanded Next Based on thousands of clinical samples Based on hundreds of clinical samples Positive VUS Negative MUTYH Carrier BRCA1 and BRCA2 VUS Rate: 3.09% Hereditary Cancer Multigene Panels GENES BRCAplus BreastNext GYNplus OvaNext ColoNext ProstateNext PancNext CancerNext BrainTumorNext MelanomaNext RenalNext PGLNext CancerNext-Exp 8 genes 17 genes 13 genes 25 genes 17 genes 14 genes 13 genes 34 genes 27 genes 8 genes 19 genes 12 genes 67 genes BARD1 BARD1 BARD1 BARD1 BARD1 BRIP1 BRIP1 BRIP1 BRIP1 BRIP1 BRIP1 MRE11A MRE11A MRE11A MRE11A MRE11A NBN NBN NBN NBN NBN NBN NBN NF1 NF1 NF1 NF1 NF1 NF1 NF1 RAD50 RAD50 RAD50 RAD50 RAD50 RAD51C RAD51C RAD51C RAD51C RAD51C RAD51C RAD51D RAD51D RAD51D RAD51D RAD51D RAD51D RAD51D ATM ATM ATM ATM ATM ATM ATM ATM PALB2 PALB2 PALB2 PALB2 PALB2 PALB2 PALB2 PALB2 PALB2 MUTYH MUTYH MUTYH MUTYH MUTYH MUTYH CHEK2 CHEK2 CHEK2 CHEK2 CHEK2 CHEK2 CHEK2 CHEK2 STK11 STK11 STK11 STK11 STK11 STK11 CDH1 CDH1 CDH1 CDH1 CDH1 CDH1 CDH1 BRCA1 BRCA1 BRCA1 BRCA1 BRCA1 BRCA1 BRCA1 BRCA1 BRCA1 BRCA2 BRCA2 BRCA2 BRCA2 BRCA2 BRCA2 BRCA2 BRCA2 BRCA2 BRCA2 PTEN PTEN PTEN PTEN PTEN PTEN PTEN PTEN PTEN PTEN PTEN TP53 TP53 TP53 TP53 TP53 TP53 TP53 TP53 TP53 TP53 TP53 TP53 TP53 MLH1 MLH1 MLH1 MLH1 MLH1 MLH1 MLH1 MLH1 MLH1 MLH1 MSH2 MSH2 MSH2 MSH2 MSH2 MSH2 MSH2 MSH2 MSH2 MSH2 MSH6 MSH6 MSH6 MSH6 MSH6 MSH6 MSH6 MSH6 MSH6 MSH6 PMS2 PMS2 PMS2 PMS2 PMS2 PMS2 PMS2 PMS2 PMS2 PMS2 EPCAM EPCAM EPCAM EPCAM EPCAM EPCAM EPCAM EPCAM EPCAM SMARCA4 SMARCA4 SMARCA4 SMARCA4 SMARCA4 APC APC APC APC APC APC BMPR1A BMPR1A BMPR1A BMPR1A SMAD4 SMAD4 SMAD4 SMAD4 CDKN2A CDKN2A CDKN2A CDKN2A CDKN2A CDKN2A CDK4 CDK4 CDK4 CDK4 GREM1 GREM1 GREM1 GREM1 POLD1 POLD1 POLD1 POLD1 POLE POLE POLE POLE HOXB13 HOXB13 HOXB13 HOXB13 DICER1 DICER1 DICER1 DICER1 DICER1 BAP1 BAP1 BAP1 BAP1 FLCN FLCN FLCN MET MET MET MITF MITF MITF MITF TSC1 TSC1 TSC1 TSC1 TSC2 TSC2 TSC2 TSC2 VHL VHL VHL VHL VHL FH FH FH FH SDHA SDHA SDHA SDHA SDHB SDHB SDHB SDHB SDHC SDHC SDHC SDHC SDHD SDHD SDHD SDHD SDHAF2 SDHAF2 SDHAF2 MAX MAX MAX RET RET RET TMEM127 TMEM127 TMEM127 MEN1 MEN1 MEN1 MEN1 AIP AIP AIP ALK ALK ALK CDKN1B CDKN1B CDKN1B NF2 NF2 NF2 PHOX2B PHOX2B PHOX2B POT1 POT1 POT1 PRKAR1A PRKAR1A PRKAR1A PTCH1 PTCH1 PTCH1 SMARCB1 SMARCB1 SMARCB1 SMARCE1 SMARCE1 SMARCE1 SUFU SUFU SUFU RB1 RB1 RB1 XRCC2 XRCC2 BLM BLM FANCC FANCC GALNT12 GALNT12 average 7-10 14.1 14.6 14 14.6 14.5 14 14.4 15.8 14.2 15 15.2 14.9 tat* * Calendar days CustomNext-Cancer allows you to choose your own combination of up to 68 genes. * Ambry’s turnaround time represents the time that it takes for Ambry to perform the requested testing. When all necessary All genes on CancerNext-Expanded plus NTHL1 are available to order. TAT is 14-21 calendar days. clinical and family history information is provided with the sample, results are typically completed within 14 days. We will notify you in the unusual event that results will take longer than 21 days. Mutation Distributions ordering the right test can provide the most accurate and comprehensive answers BreastNext* OvaNext*,1 CHEK2 BRCA1 CHEK2 BRCA2 BRCA2 RAD51C, MSH6, PMS2, RAD50, NBN, RAD51D, TP53, BARD1, BRCA1 MSH2, MLH1, MRE11A, NF1, TP53, NBN, NF1, RAD51C, ATM CDH1, PTEN, EPCAM, MRE11A, RAD51D, PTEN, CDH1, SMARCA4 MUTYH ATM PALB2 PALB2 BRIP1 < 4% BRIP1 RAD50 BARD1 < 3% CancerNext*,1 MSH6, MSH2, BRIP1, CDKN2A, CHEK2 RAD50, MLH1, NBN, TP53, RAD51C, APC, BARD1, NF1, MRE11A, PTEN, BRCA2 RAD51D, MUTYH, CDH1, EPCAM, BRCA1 ATM GREM1, BMPR1A, SMAD4, SMARCA4, STK11, POLD1, POLE PALB2 PMS2 < 4% ColoNext* BRCA2 ProstateNext* APC SMAD4, PTEN, TP53, MLH1 CDH1, STK11, GREM1, MSH2 EPCAM, POLD1, POLE ATM CHEK2 MSH6 MUTYH HOXB13 PMS2 CHEK2 BMPR1A < 4% PALB2 BRCA1 NBN Our ongoing participation in numerous research studies and collaborations is so that we can better assess clinical validity of gene-disease relationships. For more information about our research visit: ambrygen.com/ research-and-collaborations Mutation distribution data for our other hereditary cancer panels is available upon request. * Excludes MUTYH carriers, APC p.I1307K, and/or CHEK2 p.I157T depending on the genes included in the panel 1 Data not yet available for DICER1 and/or HOXB13, added March 2017 LLPO158CE1117 50339.5069_v1 | 11.07.17 15 Argonaut, Aliso Viejo, CA 92656 USA Toll Free +1.866.262.7943 Fax +1.949.900.5501 ambrygen.com.
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