2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-A next generation sequencing strategy for a comprehensive molecular diagnosis in Chronic Lymphocytic Leukemia: Mexican Experience

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A study conducted on 31 patients with Chronic Lymphocytic Leukemia (CLL) in Mexico aimed to identify biomarkers and genetic alterations associated with the disease. The study found that 87% of the patients had a biomarker with prognostic value. Out of the 31 patients, 11 had an unmutated IGHV. Among these patients, 73% had at least one other genetic alteration, and 45% had two concomitant alterations. Trisomy 12 was present in 13% of the patients with an unmutated IGHV. In two out of the six patients who were receiving treatment, an unmutated IGHV and/or a pathogenic variant in TP53 were detected. The high frequency of CLL in the northern part of Mexico may be attributed to a European genetic contribution.<br /><br />The prevalence and molecular features of CLL are similar across different populations, with recurrent chromosomal abnormalities such as deletions in 13q14, 11q, 17p, and trisomy 12. Variants in genes like SF3B1 and NOTCH1 are also observed in a significant percentage of CLL cases. The most commonly used prognostic and predictive biomarkers in CLL are pathogenic variants in TP53, deletions in 17p, and the mutational status of the IGHV.<br /><br />A next-generation sequencing (NGS) strategy was employed in this study to comprehensively diagnose CLL in Mexican patients. The NGS panel targeted 15 genes associated with CLL and identified copy number variants for trisomy 12, 13q deletion, ATM, and TP53. The Sophia DDM software was used for bioinformatic analysis, and variants were classified according to ACMG guidelines.<br /><br />The comprehensive genomic approach used in this study allowed for the detection of known and new prognostic CLL gene associations, as well as the assessment of CNVs and IGHV mutational status. This approach can optimize time and resources in the management of CLL. The study also identified trisomy 12 as a potential biomarker with worse prognosis in Mexican patients with an unmutated IGHV.<br /><br />In conclusion, this study highlights the importance of comprehensive molecular diagnosis in CLL and the potential of NGS strategies to identify biomarkers and genetic alterations associated with the disease.

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Presenting Author - Melania Abreu, MD, MS; Co-Author - Luis Villela Martínez, MD; Co-Author - Adrián Alejandro Ceballos López, MD; Co-Author - Alberto Villalobos Prieto, MD; Co-Author - Álvaro Cabrera García, MD; Co-Author - Marcela Deffis Court, MD; Co-Author - René Porfirio Amatón Tabares, MD; Co-Author - Siria María Carvajal Lohr, MD; Co-Author - Cesar Humberto Galindo Ruvalcaba, MD; Co-Author - Federico Godínez Hernández, MD; Co-Author - Yolanda Fabiola Rodríguez Muñoz, MS; Co-Author - Lizbeth Hernández Ancheyta, MS, PhD; Co-Author - Coztli Ocelotl Azotla Vilchis, MD, MS, PhD;

Meta Tag

Bioinformatics

Cancer Cytogenetics

Clinical Applications of Molecular Cytogenetics

Genetic Testing

Genotype-Phenotype Correlations

Molecular Cytogenetics

NextGen Sequencing

Sequencing

Variant Detection

Co-Author Luis Villela Martínez, MD

Co-Author Adrián Alejandro Ceballos López, MD

Co-Author Alberto Villalobos Prieto, MD

Co-Author Álvaro Cabrera García, MD

Co-Author Marcela Deffis Court, MD

Co-Author René Porfirio Amatón Tabares, MD

Co-Author Siria María Carvajal Lohr, MD

Co-Author Cesar Humberto Galindo Ruvalcaba, MD

Co-Author Federico Godínez Hernández, MD

Co-Author Yolanda Fabiola Rodríguez Muñoz, MS

Co-Author Lizbeth Hernández Ancheyta, MS, PhD

Co-Author Coztli Ocelotl Azotla Vilchis, MD, MS, PhD

Presenting Author Melania Abreu, MD, MS

Keywords

Chronic Lymphocytic Leukemia

CLL

biomarkers

genetic alterations

prognostic value

unmutated IGHV

genetic contribution

chromosomal abnormalities

pathogenic variants

next-generation sequencing