Haploseek: a 24-hour all-in-one method for preimplantation genetic diagnosis (PGD) of monogenic disease and aneuploidy

Backenroth, Daniel; Zahdeh, Fouad; Kling, Yehuda; Peretz, Aharon; Rosen, Tzvia; Kort, Dina; Zeligson, Sharon; Dror, T.; Kirshberg, Sophie; Burak, Efrat; Segel, Reeval; Levy‐Lahad, Ephrat; Zangen, David; Altarescu, Gheona; Carmi, Shai; Zeevi, David A.

doi:10.1038/s41436-018-0351-7

Cited by 38 publications

(60 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The conclusion of this study was that robust identification of CNVs was highly feasible with low-coverage WGS 43 . In another study, low-coverage WGS also found successful application in preimplantation genetic diagnosis of monogenic disease 44 .…”

Section: Discussionmentioning

confidence: 99%

Whole genome analysis identifies the association of TP53 genomic deletions with lower survival in Stage III colorectal cancer

Hummelen

Kubit

et al. 2020

Sci Rep

View full text Add to dashboard Cite

DnA copy number aberrations (cnA) are frequently observed in colorectal cancers (cRc). there is an urgent need for cnA-based biomarkers in clinics,. n for Stage iii cRc, if combined with imaging or pathologic evidence, these markers promise more precise care. We conducted this Stage III specific biomarker discovery with a cohort of 134 CRCs, and with a newly developed high-efficiency CNA profiling protocol. Specifically, we developed the profiling protocol for tumor-normal matched tissue samples based on low-coverage clinical whole-genome sequencing (WGS). We demonstrated the protocol's accuracy and robustness by a systematic benchmark with microarray, high-coverage wholeexome and-genome approaches, where the low-coverage WGS-derived cnA segments were highly accordant (pcc >0.95) with those derived from microarray, and they were substantially less variable if compared to exome-derived segments. A lasso-based model and multivariate cox regression analysis identified a chromosome 17p loss, containing the TP53 tumor suppressor gene, that was significantly associated with reduced survival (p = 0.0139, HR = 1.688, 95% CI = [1.112-2.562]), which was validated by an independent cohort of 187 Stage III CRCs. In summary, this low-coverage WGS protocol has high sensitivity, high resolution and low cost and the identified 17p-loss is an effective poor prognosis marker for Stage iii patients. Extensive copy number aberrations (CNA) are a hallmark of cancers with genome instability and are observed among a wide variety of epithelial malignancies originating from the colon, breast, cervix, prostate, bladder and stomach 1. High levels of CNAs are associated with cancer progression and poor prognosis. Thus, there is general interest in profiling CNAs as potential biomarkers associated with specific clinical outcome. The focus of our study was colorectal cancer (CRC), the third most common cancer worldwide , with ~1.8 million estimated new cases yearly. The majority of CRCs demonstrates an extensive CNAs and as a result, are designated as belonging to the chromosomal-instability (CIN) molecular subtype. To accurately profile CNAs and evaluate their prognostic significance in CRC, a variety of methods have been used which include karyotyping, fluorescent in-situ hybridization (FISH), and chromosomal microarrays, such as comparative genomic hybridization (CGH) arrays and single nucleotide polymorphisms (SNP) arrays. Citing some examples, with karyotyping, Bardi et al. found that loss of chromosome 18 was correlated with shorter overall survival in early-stage patients (N = 150) 2. Personeni et al. 3 using FISH identified that changes in EGFR copy number predicted overall survival for EGFR-targeted therapy in a metastatic CRC cohort (N = 87). Using SNP-arrays, Sheffer et al. identified deletions of 8p, 4p, and 15q were associated with poor survival in a mixed-stage cohort (N = 130) 4. Other microarray-based studies 5-7 using smaller numbers of patients (N <100) identified various CNAs associated with poor survival that included sub-...

show abstract

Section: Discussionmentioning

confidence: 99%

Whole genome analysis identifies the association of TP53 genomic deletions with lower survival in Stage III colorectal cancer

Hummelen

Kubit

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In another study, low-coverage WGS also found successful application in preimplantation genetic diagnosis of monogenic disease 39 .…”

Section: Discussionmentioning

confidence: 99%

Whole genome analysis identifies the association of TP53 genomic deletions with lower survival in Stage III colorectal cancer

Xia

Hummelen

Kubit

et al. 2019

Preprint

View full text Add to dashboard Cite

DNA copy number aberrations (CNA) were frequently observed in colorectal cancers (CRC).There is an urgent call for CNA-based biomarkers in clinics, in particular for Stage III CRC, if combined with imaging or pathologic evidence, promise more precise care at the timing. We conducted this Stage III specific biomarker discovery with a cohort of 134 CRCs, and with a newly developed high-efficiency CNA profiling protocol. Specifically, we developed the profiling protocol for tumor-normal matched tissue samples based on low-coverage clinical wholegenome sequencing (WGS). We demonstrated the protocol's accuracy and robustness by a systematic benchmark with microarray, high-coverage whole-exome and -genome approaches, where the low-coverage WGS-derived CNA segments were highly accordant (PCC>0.95) with those derived from microarray, and they were substantially less variable if compared to exome-derived segments. A lasso-based model and multivariate cox regression analysis identified a chromosome 17p loss, containing the TP53 tumor suppressor gene, that was significantly associated with reduced survival (P=0.0139, HR=1.688, 95% CI = [1.112-2.562]), which was validated by an independent cohort of 187 Stage III CRCs. In summary, the new low-coverage WGS protocol has high sensitivity, high resolution and low cost and the identified 17p-loss is an effective poor prognosis marker for Stage III patients.

show abstract

“…Both SNP arrays and NGS maximize the genetic information available from each embryo with also reference to chromosome copy number in the context of PGT-A [51]. In earlier applications, the testing of two different biopsies was performed to enable PGT-M with aneuploidy screening but, more recently, this has been achieved from the same biopsy and whole genome amplification product (WGA) in family-specific or universal protocols, improving pregnancy rates [52]. The combination of PGT-M with HLA typing and aneuploidy screening was performed in a study using WGA that was followed by aCGH and multiplex PCR from different portions of the same WGA product.…”

Section: Overview Of Pgt-hla Methodologymentioning

confidence: 99%

Preimplantation Genetic Testing for HLA-matching: An Overview of Clinical Application and Utility

Kakourou¹,

Mamas²,

Vrettou³

et al. 2019

obm genet

View full text Add to dashboard Cite

Preimplantation Genetic Testing for Human Leucocyte Antigen-matching (PGT-HLA), first reported in 2001, has been one of the most controversial PGT applications. The procedure aims to identify an embryo that is not only healthy but also HLA-matched with a sibling in the family in need of hematopoietic stem cell transplantation (HSCT), considering that sibling HSCT stands the highest chance of success in comparison to alternative approaches of donor selection. HLA-typing can be performed with or without PGT for the exclusion of a monogenic disorder (PGT-M). The diagnostic PGT approach has greatly evolved over the years. HLA haplotyping by linkage analysis has been the most commonly applied generic approach to date but nowadays newer techniques (SNP arrays, NGS) are also being applied. PGT-HLA is a complex procedure that must be very well orchestrated between specialists of many different disciplines to ensure that successful HSCT is completed in time for the maximum benefit of the recipient. This review discusses the procedure and methodology of PGT, clinical application, and utility of PGT-HLA, and underlines how, despite the limitations, it has been a successful and realistic approach for many couples.

show abstract

Haploseek: a 24-hour all-in-one method for preimplantation genetic diagnosis (PGD) of monogenic disease and aneuploidy

Cited by 38 publications

References 19 publications

Whole genome analysis identifies the association of TP53 genomic deletions with lower survival in Stage III colorectal cancer

Whole genome analysis identifies the association of TP53 genomic deletions with lower survival in Stage III colorectal cancer

Whole genome analysis identifies the association of TP53 genomic deletions with lower survival in Stage III colorectal cancer

Preimplantation Genetic Testing for HLA-matching: An Overview of Clinical Application and Utility

Contact Info

Product

Resources

About