ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia—update on methodological approaches and results interpretation

Malčíková, Jitka; Tausch, Eugen; Rossi, Davide; Sutton, Lesley-Ann; Soussi, Thierry; Zenz, Thorsten; Kater, Arnon P.; Niemann, Carsten Utoft; González, David; Davi, Frédéric; Díaz, Marcos González; Moreno, Carolina; Gaïdano, Gianluca; Stamatopoulos, Kostas; Rosenquist, Richard; Stilgenbauer, S.; Ghia, Paolo; Pospı́šilová, Šárka

doi:10.1038/s41375-017-0007-7

Cited by 154 publications

(198 citation statements)

References 55 publications

Supporting

Mentioning

193

Contrasting

Unclassified

Order By: Relevance

“…Whereas previous nanopore sequencing studies in CLL focussed only on the detection of SNVs 37 , we were able to identify both SNVs and indels, as well as accurately defining the IgHV region, a patient-specific locus subject to somatic hypermutation. The unrestricted read length of nanopore sequencing enabled us to sequence the full exonic region of TP53, along with full length IgHV genes, in accordance with the current ERIC guidelines for screening CLL 31,38 .…”

Section: Discussionmentioning

confidence: 99%

The diagnostic chronic lymphocytic leukaemia genome by nanopore sequencing

Burns

DiSalvo-Williams

Bruce

et al. 2019

Preprint

View full text Add to dashboard Cite

Chronic lymphocytic leukaemia (CLL) is characterised by considerable clinical and biological heterogeneity, with specific recurrent genomic alterations, including TP53 mutations, deletions of chromosome 17p, and IgHV mutational status, impacting on response to chemo-immunotherapy and targeted agents. Consequently, diagnostic screening for these predictive biomarkers is recommended in both national and international clinical guidelines. Current conventional methods, including fluorescent in-situ hybridisation and Sanger sequencing, exhibit shortcomings in terms of cost, speed and sensitivity, and even second-generation sequencing methods encounter technical limitations imposed by short-read lengths and bio-informatics analysis. The MinION platform from Oxford Nanopore Technologies generates exceptionally long (1-100kbp) read lengths in a short period of time and at low cost, making it a good candidate for diagnostic testing. In this paper, we present a nanopore-based CLLspecific screening assay, to simultaneously screen for both TP53 mutations and del17p13.1, as well as determining the IgHV mutation status for a single patient in one sequencing run. We sequenced 11 CLL patients and were able to generate a full diagnostic dataset for all. We identified somatic SNVs and indels in the coding region of TP53, and demonstrate that, following error correction of the data, we could accurately define the somatically hypermutated IgHV region in all patients. We also demonstrated the ability of the MinION platform to detect large-scale genomic deletions through low-coverage whole-genome sequencing. We conclude that nanopore sequencing has the potential to provide accurate, low-cost and rapid diagnostic information, which could be applied to other cancer types.

show abstract

Section: Discussionmentioning

confidence: 99%

The diagnostic chronic lymphocytic leukaemia genome by nanopore sequencing

Burns

DiSalvo-Williams

Bruce

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…The clinical utility of TP53 gene analysis is indisputable (Leroy et al., ). In CLL, analysis of TP53 aberrations has been incorporated into routine clinical diagnostics to improve patient stratification and optimize therapeutic decisions (Malcikova et al., ). Other cancers such as AML will also benefit from an accurate TP53 status analysis (Döhner et al., ).…”

Section: Discussion and Future Prospectsmentioning

confidence: 99%

Seshat: A Web service for accurate annotation, validation, and analysis ofTP53variants generated by conventional and next-generation sequencing

Tikkanen¹,

Leroy

Fournier

et al. 2018

Human Mutation

Self Cite

View full text Add to dashboard Cite

Accurate annotation of genomic variants in human diseases is essential to allow personalized medicine. Assessment of somatic and germline TP53 alterations has now reached the clinic and is required in several circumstances such as the identification of the most effective cancer therapy for patients with chronic lymphocytic leukemia (CLL). Here, we present Seshat, a Web service for annotating TP53 information derived from sequencing data. A flexible framework allows the use of standard file formats such as Mutation Annotation Format (MAF) or Variant Call Format (VCF), as well as common TXT files. Seshat performs accurate variant annotations using the Human Genome Variation Society (HGVS) nomenclature and the stable TP53 genomic reference provided by the Locus Reference Genomic (LRG). In addition, using the 2017 release of the UMD_TP53 database, Seshat provides multiple statistical information for each TP53 variant including database frequency, functional activity, or pathogenicity. The information is delivered in standardized output tables that minimize errors and facilitate comparison of mutational data across studies. Seshat is a beneficial tool to interpret the ever-growing TP53 sequencing data generated by multiple sequencing platforms and it is freely available via the TP53 Website, http://p53.fr or directly at http://vps338341.ovh.net/.

show abstract

“…This is also true for cancer, for which it is important to rapidly detect certain Copy Number Variations (CNVs), such as the 17p deletion, a recurrent abnormality in Chronic Lymphocytic Leukemia (CLL), with major therapeutic implications. Because this acquired chromosomal abnormality directly impairs the TP53 gene [2,3], it is now recommended to test this CNV before each treatment for CLL [4]. Indeed, TP53 alterations in CLL are responsible for primary resistance to fludarabine and survival of such patients is clearly improved by new-targeted therapies, such as ibrutinib [5,6].…”

Section: Introductionmentioning

confidence: 99%

CovCopCan: An efficient tool to detect Copy Number Variation from amplicon sequencing data in inherited diseases and cancer

Derouault¹,

Chauzeix

Rizzo

et al. 2020

PLoS Comput Biol

View full text Add to dashboard Cite

Molecular diagnosis is an essential step of patient care. An increasing number of Copy Number Variations (CNVs) have been identified that are involved in inherited and somatic diseases. However, there are few existing tools to identify them among amplicon sequencing data generated by Next Generation Sequencing (NGS). We present here a new tool, CovCopCan, that allows the rapid and easy detection of CNVs in inherited diseases, as well as somatic data of patients with cancer, even with a low ratio of cancer cells to healthy cells. This tool could be very useful for molecular geneticists to rapidly identify CNVs in an interactive and user-friendly way. This is a PLOS Computational Biology Software paper.PLOS Computational Biology | https://doi.

show abstract

ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia—update on methodological approaches and results interpretation

Cited by 154 publications

References 55 publications

The diagnostic chronic lymphocytic leukaemia genome by nanopore sequencing

The diagnostic chronic lymphocytic leukaemia genome by nanopore sequencing

Seshat: A Web service for accurate annotation, validation, and analysis ofTP53variants generated by conventional and next-generation sequencing

CovCopCan: An efficient tool to detect Copy Number Variation from amplicon sequencing data in inherited diseases and cancer

Contact Info

Product

Resources

About