TumorNext-HRD

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 inhibitors^1-11

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. Suspect variant calls of germline origin other than those classified as "likely benign" or "benign" detected on the paired analysis are verified by Sanger sequencing. The BRCA2 Portuguese founder mutation, c.156_157insAlu (also known as 384insAlu) is detected by  multiplex ligation-dependent probe amplification (MLPA). Germline gross deletion/duplication analysis of all sequenced genes is performed using targeted chromosomal microarray with confirmatory MLPA when applicable. 

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