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However, the mutational landscape of Mexican children with preB\u2010ALL has not yet been thoroughly explored and defined in terms of the clinical significance. We used a custom\u2010designed next\u2010generation sequencing exome panel, along with high\u2010resolution chromosome microarrays and gene fusion\u2010targeted assays, to characterize the mutational landscape of 73 Mexican children with preB\u2010ALL, exploring the profile of clinically significant variants. We classified the variants following the AMP\u2010ASCO\u2010CAP 2017 and ACMG\u2010CG 2019 guidelines recommendations. The mutational landscape includes a broad molecular spectrum of variants affecting cell cycle regulation, B\u2010cell development, kinase signaling, and epigenetic regulation genes. Tier 1 diagnostic variants allowed the identification of pre\u2010B ALL genetic subtypes, diminishing the preB\u2010ALL NOS group from 63% to 37%. Furthermore, 37% of cases presented Tier 1 variants conferring intermediate to adverse prognoses (primarily involving\n                    <jats:italic>CRLF2<\/jats:italic>\n                    gene fusions, as well as\n                    <jats:italic>PAX5, IKZF1,<\/jats:italic>\n                    and\n                    <jats:italic>TP53<\/jats:italic>\n                    inactivating mutations). Notably, these patients exhibited high\u2010risk clinical features and a lower event free survival rate than patients without these variants (60% versus 41.2%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.046; 95% CI). Between 19% and 42% of patients had Tier 2 variants targetable with JAK\u2010STAT or RAS\u2010MAPK signaling inhibitors. These patients showed a lower overall survival rate than patients without these variants (64% versus 90%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.048; 95% CI). Tier 1 potential germline variants in cancer predisposition genes (mainly\n                    <jats:italic>BRCA1\/2<\/jats:italic>\n                    and\n                    <jats:italic>CHEK2)<\/jats:italic>\n                    were observed in 10% of patients, some of whom had a family history of cancer. This highlights the importance of genetic counseling for patients and their families. Finally, 33% of patients had Tier 3 variants that were predicted to be deleterious and potentially upgraded to pathogenic with plausible clinical relevance. In conclusion, the mutational landscape analysis revealed variants useful for oncologic management and genetic counseling of Mexican children with preB\u2010ALL.\n                  <\/jats:p>","DOI":"10.1002\/2056-4538.70107","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T08:07:26Z","timestamp":1785917246000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic profiling of Mexican patients with B\u2010cell precursor acute lymphoblastic leukemia reveals clinically significant somatic and potential germline variants"],"prefix":"10.1002","volume":"12","author":[{"given":"Daniel","family":"Mart\u00ednez Anaya","sequence":"first","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y C\u00e1ncer Instituto Nacional de Pediatr\u00eda  Mexico City Mexico"},{"name":"Posgrado en Ciencias Biol\u00f3gicas, Facultad de Medicina Universidad Nacional Aut\u00f3noma de M\u00e9xico  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda del Roc\u00edo","family":"Ju\u00e1rez\u2010Vel\u00e1zquez","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y C\u00e1ncer Instituto Nacional de Pediatr\u00eda  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulises","family":"Ju\u00e1rez Figueroa","sequence":"additional","affiliation":[{"name":"Laboratorio de Citogen\u00e9tica Instituto Nacional de Pediatr\u00eda  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Dean","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics National Cancer Institute  Rockville MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Consuelo","family":"Salas Labad\u00eda","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y C\u00e1ncer Instituto Nacional de Pediatr\u00eda  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Valladares Coyotecatl","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y C\u00e1ncer Instituto Nacional de Pediatr\u00eda  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Reyes Le\u00f3n","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y C\u00e1ncer Instituto Nacional de Pediatr\u00eda  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma","family":"L\u00f3pez Santiago","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda Instituto Nacional de Pediatr\u00eda  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Ju\u00e1rez Villegas","sequence":"additional","affiliation":[{"name":"Servicio de Hemato\u2010Oncolog\u00eda Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Zapata Tarr\u00e9s","sequence":"additional","affiliation":[{"name":"Comisi\u00f3n Coordinadora de Institutos Nacionales de Salud y Hospitales de Alta Especialidad  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5662-6991","authenticated-orcid":false,"given":"Patricia","family":"P\u00e9rez\u2010Vera","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y C\u00e1ncer Instituto Nacional de Pediatr\u00eda  Mexico City 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