TumorNext-HRD

Women with ovarian cancer need a reliable test to assess for hereditary cancer and guide targeted treatment decisions. TumorNext-HRD is a paired tumor and germline analysis of BRCA1 and BRCA2 plus 9 additional genes in the homologous recombination repair pathway. Looking at both the tumor and germline can provide more complete information to guide ovarian cancer management. 
Quick Reference
Test Code: 9810 Test Name: TumorNext- BRCA TAT 3-4 weeks Genes: 2
Test Code: 9811 Test Name: TumorNext- HRD TAT 3-4 weeks Genes: 11

Ordering Options

We now offer single site analysis (SSA) at no additional cost to family members

following single gene or panel testing* of the first family member (proband) within 90 days of the original Ambry report date.

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*excludes Secondary Findings and SNP Array tests

Why Is This Important?

TumorNext-HRD can detect and differentiate between germline and somatic mutations in homologous recombination repair genes including BRCA1 and BRCA2 so that you can:

  1. Identify ovarian cancer patients who are at an increased risk for other cancers
  2. Identify patients who have family members that may be at a significantly increased risk for cancer and clarify management recommendations
  3. Learn if there are variants in the tumor that may cause homologous recombination deficiency (HRD)
  4. Guide targeted treatment, such as with PARP inhibitors1-11

 

When To Consider Testing

All patients diagnosed with ovarian cancer may benefit from TumorNext-HRD

  • SGO recommends that all women diagnosed with epithelial ovarian, fallopian tube, and peritoneal cancers should consider genetic testing, even in the absence of a family history of cancer.12
  • Newly Diagnosed Ovarian Cancer: Maintenance therapy with a PARP inhibitor may be an appropriate treatment for women with a BRCA1/2 mutation6
  • Recurrent Platinum Sensitive Ovarian Cancer: PARP inhibitor therapy may be beneficial for BRCA1/2 carriers

Test Description

TumorNext-HRD targets detection of germline and somatic variants in genes in the homologous recombination repair pathway (ATM, BARD1, BRCA1, BRCA2, BRIP1, CHEK2, MRE11A, NBN, PALB2, RAD51C, and RAD51D). Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen(s) using standardized methodology and quantified. For FFPE section, one thin (5 micron) tissue section is first cut and stained with hematoxylin and eosin (H&E). The H&E slide is examined by a pathologist to determine tissue quantity/quality and neoplastic cellularity (20% minimum). Sequence enrichment of the germline and tumor sample for the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology using long biotinylated oligonucleotide probes followed by polymerase chain reaction (PCR) and Next-Generation sequencing (NGS). The bioinformatics pipeline performs paired analysis of sequence data from both tumor and germline specimens to differentiate variants of somatic origin from germline origin. Optimized variant calling filters require a read coverage depth of >100X for tumor and > 20X for matched control blood DNA. For molecular analysis of variants of germline origin only, additional Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Germline 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 (Mu W et al. J Mol Diagn. 2016 Oct 4). The BRCA2 Portuguese founder mutation, c.156_157insAlu (also known as 384insAlu) is detected by next generation sequencing and confirmed by multiplex ligation-dependent probe amplification (MLPA) or PCR and agarose gel electrophoresis. Germline gross deletion/duplication analysis for 11 of the genes (excluding PMS2) is performed using a custom pipeline based on NGS data and/or targeted chromosomal microarray with confirmatory MLPA when applicable.

References: 

  1. Hennessy BTJ, et al. JCO. 2010 Aug 1;28(22):3570-6
  2. Pennington KP et al. Clin Cancer Res. 2014 Feb 1;20(3):764-75
  3. Banerjee S & Kaye S. Curr Oncol Rep. 2011 Dec;13(6):442-9
  4. Burgess M & Puhalla S. Front Oncol. 2014 Feb 27;4:19
  5. Yamamoto KN et al. PLoS One. 2014 Aug 26;9(8):e105724
  6. Moore et al. NEJM 2018 Oct 21 (Epub ahead of print)
  7. Ledermann, et al. Lancet Oncol. 2014;15(8):852-861
  8. Pujade-Lauraine, et al. Lancet Oncol. 2017;18:1274-1284
  9. Mirza, et al. N Engl J Med. 2016;375:2154-2164
  10. Coleman RL, et al. Lancet. 2017 Oct 28;390(10106):1949-1961
  11. Swisher, et al. Lancet Oncology 2017 18: 75-87
  12. SGO Clinical Practice Statement: Genetic Testing for Ovarian Cancer. October 2014
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