ABSTRACT 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.

A leucemia linfocítica crônica (CLL) apresenta incidência variável de anomalias de cariótipo devido às dificuldades em se obter mitose para análise. Desde a introdução da citogenética molecular (FISH = hibridação in situ por fluorescência) usando sonda centromérica para o cromossomo 12 foi possível detectar uma maior porcentagem de casos com trissomia 12. O objetivo deste trabalho foi de detectar trissomia 12 por FISH (sonda alfa satélite) em 13 pacientes com CLL cujos cariótipos por banda G haviam sido normais ou sem resultado. Três pacientes apresentaram trissomia 12 por este método com uma porcentagem de células trissômicas variando de 55,5 a 79%, demonstrando que a FISH é um método sensível e altamente específico para detecção de trissomia 12.

Chronic lymphocytic leukemia (CLL) presents a varying incidence of karyotypic abnormalities whose detection is complicated by difficulties in obtaining mitosis for analysis in this type of mature lymphocyte disorder. Since the introduction of molecular cytogenetics (FISH = fluorescent in situ hybridization), applying centromeric probes for chromosome 12 has made it possible to detect a higher percentage of trisomy 12 cases. The objective of the present study was to detect trisomy 12 by FISH (alpha satellite probe) in 13 patients with CLL whose karyotypes by G-banding were either normal or inadequate. Using this method trisomy 12 was detected in three patients in a percentage of positive cells varying from 55.5% to 79%, showing that FISH is a sensitive and highly specific method for trisomy detection and should be routinely performed when the karyotype is normal.