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

• Published in: Leukemia Vol. 32; no. 5; pp. 1070 - 1080
• Main Authors: Malcikova, J., Tausch, E., Rossi, D., Sutton, L. A., Soussi, T., Zenz, T., Kater, A. P., Niemann, C. U., Gonzalez, D., Davi, F., Gonzalez Diaz, M., Moreno, C., Gaidano, G., Stamatopoulos, K., Rosenquist, R., Stilgenbauer, S., Ghia, P., Pospisilova, S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 2018; Nature Publishing Group; Springer Nature
• Subjects: 45/23; 631/67/1990/283/1895; 692/308/575; Apoptosis; B-cell receptor; Biochemistry, Molecular Biology; Cancer; Cancer Research; Chromosome 17; Chronic lymphocytic leukemia; Clonal deletion; Critical Care Medicine; Defects; Diagnostic systems; Gene deletion; Genomics; Hematology; Human health and pathology; Intensive; Internal Medicine; Leukemia; Life Sciences; Lymphatic leukemia; Lymphocyte receptors; Lymphocytes B; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Mutation; Oncology; p53 Protein; Patients; Review; Review Article
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/s41375-017-0007-7

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.