TP53 mutation analysis in chronic lymphocytic leukemia: comparison of different detection methods

Kantorová, Barbara; Malčíková, Jitka; Šmardová, Jana; Pavlová, Šárka; Trbušek, Martin; Tom, Nikola; Plevová, Karla; Tichý, Boris; Truong, Sim; Divíšková, Eva; Kotašková, Jana; Oltová, Alexandra; Patten, Nancy; Brychtová, Yvona; Doubek, Michael; Mayer, Jiřı́; Pospı́šilová, Šárka

doi:10.1007/s13277-014-2971-0

Cited by 11 publications

(10 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous commercially available ready-to-use analytical kits include the TP53 gene, and ERIC is conducting a multi-center collaborative effort to assess and compare various pre-designed and custom gene panel technologies. Previous studies exploring the inter-reproducibility of targeted NGS and Sanger sequencing for TP53 analysis demonstrated very good correlation of the results, specifically showing that all variants detected by Sanger sequencing are also detectable by NGS [ 22 , 23 , 32 – 35 ]. A recent study also showed an excellent correlation between the results obtained from two different NGS platforms, namely, the Ion PGM (ThermoFisher) and the MiSeq (Illumina) [ 33 ].…”

Section: Procedures Descriptionmentioning

confidence: 97%

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

Malčíková¹,

Tausch²,

Rossi³

et al. 2018

Leukemia

176

207

View full text Add to dashboard Cite

In chronic lymphocytic leukemia (CLL), TP53 gene defects, due to deletion of the 17p13 locus and/or mutation(s) within the TP53 gene, are associated with resistance to chemoimmunotherapy and a particularly dismal clinical outcome. On these grounds, analysis of TP53 aberrations has been incorporated into routine clinical diagnostics to improve patient stratification and optimize therapeutic decisions. The predictive implications of TP53 aberrations have increasing significance in the era of novel targeted therapies, i.e., inhibitors of B-cell receptor (BcR) signaling and anti-apoptotic BCL2 family members, owing to their efficacy in patients with TP53 defects. In this report, the TP53 Network of the European Research Initiative on Chronic Lymphocytic Leukemia (ERIC) presents updated recommendations on the methodological approaches for TP53 mutation analysis. Moreover, it provides guidance to ensure that the analysis is performed in a timely manner for all patients requiring treatment and that the data is interpreted and reported in a consistent, standardized, and accurate way. Since next-generation sequencing technologies are gaining prominence within diagnostic laboratories, this report also offers advice and recommendations for the interpretation of TP53 mutation data generated by this methodology.

show abstract

Section: Procedures Descriptionmentioning

confidence: 97%

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

Malčíková¹,

Tausch²,

Rossi³

et al. 2018

Leukemia

176

207

View full text Add to dashboard Cite

show abstract

“…Techniques frequently used for assessing TP53 status in CLL include FISH for del(17p), Sanger sequencing, and next-generation sequencing for TP53 mutations ( Table 2 ). 27 , 35 , 74 , 75 As TP53 mutations are associated with a poor prognosis independently of the presence of del(17p), 7 it is important to assess for TP53 mutation status using a sequencing technique. 27 , 35 …”

Section: Introductionmentioning

confidence: 99%

“…Next-generation sequencing technologies include targeted next-generation sequencing, which has good correlation with Sanger sequencing in comparison studies 12 , 28 , 31 , 35 , 75 , 78 and detects low-frequency mutations below the threshold for Sanger sequencing. 38 , 79 – 81 The sensitivity threshold varies depending on a number of variables, including the hardware, methods used for testing and the analytical pipeline, and should be defined by each laboratory using standardized criteria or equivalent medical laboratory standards.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

TP53 aberrations in chronic lymphocytic leukemia: an overview of the clinical implications of improved diagnostics

et al. 2018

Self Cite

View full text Add to dashboard Cite

Chronic lymphocytic leukemia is associated with a highly heterogeneous disease course in terms of clinical outcomes and responses to chemoimmunotherapy. This heterogeneity is partly due to genetic aberrations identified in chronic lymphocytic leukemia cells such as mutations of TP53 and/or deletions in chromosome 17p [del(17p)], resulting in loss of one TP53 allele. These aberrations are associated with markedly decreased survival and predict impaired response to chemoimmunotherapy thus being among the strongest predictive markers guiding treatment decisions in chronic lymphocytic leukemia. Clinical trials demonstrate the importance of accurately testing for TP53 aberrations [both del(17p) and TP53 mutations] before each line of treatment to allow for appropriate treatment decisions that can optimize patients’ outcomes. The current report reviews the diagnostic methods to detect TP53 disruption better, the role of TP53 aberrations in treatment decisions and current therapies available for patients with chronic lymphocytic leukemia carrying these abnormalities. The standardization in sequencing technologies for accurate identification of TP53 mutations and the importance of continued evaluation of TP53 aberrations throughout initial and subsequent lines of therapy remain unmet clinical needs as new therapeutic alternatives become available.

show abstract

“…The spectrum of mutations identified by this method was the same as that of the DHPLC analysis followed by the Sanger sequencing. 48 …”

Section: Introductionmentioning

confidence: 99%

Detection of somatic TP53 mutations and 17p deletions in patients with chronic lymphocytic leukemia: a review of the current methods

Chauffaille

Zalcberg

Barreto

et al. 2020

Hematology, Transfusion and Cell Therapy

View full text Add to dashboard Cite

Chronic lymphocytic leukemia is the most common hematologic malignancy among adults in Western countries. Several studies show that somatic mutations in the TP53 gene are present in up to 50% of patients with relapsed or refractory chronic lymphocytic leukemia. This study aims to review and compare the methods used to detect somatic TP53 mutations and/or 17p deletions and analyze their importance in the chronic lymphocytic leukemia diagnosis and follow-up. In chronic lymphocytic leukemia patients with refractory or recurrent disease, the probability of clonal expansion of cells with the TP53 mutation and/or 17p deletion is very high. The studies assessed showed several methodologies able to detect these changes. For the 17p deletion, the chromosome G-banding (karyotype) and interphase fluorescence in situ hybridization are the most sensitive. For somatic mutations involving the TP53 gene, moderate or high-coverage read next-generation sequencing and Sanger sequencing are the most recommended ones. The TP53 gene mutations represent a strong adverse prognostic factor for patient survival and treatment resistance in chronic lymphocytic leukemia. Patients carrying low-proportion TP53 mutation (less than 20–25% of all alleles) remain a challenge to these tests. Thus, for any of the methods employed, it is essential that the laboratory conduct its analytical validation, documenting its accuracy, precision and sensitivity/limit of detection.

show abstract

TP53 mutation analysis in chronic lymphocytic leukemia: comparison of different detection methods

Cited by 11 publications

References 36 publications

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

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

TP53 aberrations in chronic lymphocytic leukemia: an overview of the clinical implications of improved diagnostics

Detection of somatic TP53 mutations and 17p deletions in patients with chronic lymphocytic leukemia: a review of the current methods

Contact Info

Product

Resources

About