{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T14:51:28Z","timestamp":1773672688050,"version":"3.50.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"\n Background<\/jats:title>\n \n Deleterious\n CHEK2<\/jats:italic>\n germline variants (GVs) are moderate-penetrance risk alleles that predispose individuals to adult-onset neoplasms. However, their association with childhood-onset cancers, such as B-cell precursor acute lymphoblastic leukemia (pre-B ALL), remains unexplored.\n <\/jats:p>\n <\/jats:sec>\n \n Aim<\/jats:title>\n \n To describe the mutational profile of\n CHEK2<\/jats:italic>\n GVs in a cohort of Mexican children diagnosed with pre-B ALL and review the mutational landscape of\n CHEK2<\/jats:italic>\n GVs in children with pre-B ALL.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Next-generation exome sequencing was performed on 73 Mexican children with pre-B ALL. Clinical and genetic features of\n CHEK2<\/jats:italic>\n GVs carriers have been described. Associations between\n CHEK2<\/jats:italic>\n GVs and predisposition to pre\u2013B ALL were evaluated using the MCPS population datasets as control groups. In addition, a literature review was conducted to investigate the potential link between\n CHEK2<\/jats:italic>\n germline variants and pre-B ALL. Finally, an in silico analysis was performed using bioinformatic tools and protein modeling to predict the functional and structural effects of these variants.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n CHEK2<\/jats:italic>\n GVs were identified in four patients with high-risk pre-B ALL, two carried likely pathogenic variants (2.7%) and two carried variants of uncertain significance (2.7%). Three of these patients died due to disease progression, and two had a family history consistent with the\n CHEK2<\/jats:italic>\n cancer predisposition spectrum. Two unrelated cases carried the likely pathogenic\n CHEK2<\/jats:italic>\n p.Leu236Pro variant. When compared with the Indigenous Mexican stratum of the MCPS database, this variant was associated with pre\u2013B ALL predisposition (unadjusted OR, 5.48; 95% CI, 1.34\u201322.37). Including previously reported cases, a total of 34 individuals with pre\u2013B ALL carrying 20 distinct\n CHEK2<\/jats:italic>\n GVs were identified in the literature. Most variants were population-specific and predicted to impair protein function or structural stability. Structural modeling suggested that the recurrent\n CHEK2<\/jats:italic>\n p.Leu236Pro variant may introduce steric hindrance affecting protein dimerization.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our findings and those described in the literature suggest that\n CHEK2<\/jats:italic>\n may play a role in the germline origin of childhood pre-B ALL in specific populations. However, this study provides preliminary evidence of pre-B ALL predisposition in Mexican children with\n CHEK2<\/jats:italic>\n GVs that needs replication in a larger cohort to obtain accurate estimations.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fonc.2026.1751793","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T13:35:46Z","timestamp":1773668146000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CHEK2 germline variants in B-cell precursor acute lymphoblastic leukemia: findings in Mexican pediatric patients"],"prefix":"10.3389","volume":"16","author":[{"given":"Daniel","family":"Mart\u00ednez Anaya","sequence":"first","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y C\u00e1ncer, Instituto Nacional de Pediatr\u00eda","place":["Mexico City, Mexico"]},{"name":"Posgrado en Ciencias Biol\u00f3gicas, Unidad de Posgrado, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad Universitaria","place":["Mexico City, Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliana","family":"Fern\u00e1ndez Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Molecular, Instituto Nacional de Pediatr\u00eda","place":["Mexico City, Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian","family":"Valladares Coyotecatl","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y C\u00e1ncer, Instituto Nacional de Pediatr\u00eda","place":["Mexico City, Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulises","family":"Ju\u00e1rez Figueroa","sequence":"additional","affiliation":[{"name":"Laboratorio de Citogen\u00e9tica, Instituto Nacional de Pediatr\u00eda","place":["Mexico City, Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Dean","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute","place":["Rockville, MD, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Ju\u00e1rez Villegas","sequence":"additional","affiliation":[{"name":"Servicio de Hemato-Oncolog\u00eda, Hospital Infantil de M\u00e9xico Federico G\u00f3mez","place":["Mexico City, Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Zapata Tarr\u00e9s","sequence":"additional","affiliation":[{"name":"Comisi\u00f3n Coordinadora de Institutos Nacionales de Salud y Hospitales de Alta Especialidad","place":["Mexico City, Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norma","family":"L\u00f3pez Santiago","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda, Instituto Nacional de Pediatr\u00eda","place":["Mexico City, Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"P\u00e9rez-Vera","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y C\u00e1ncer, Instituto Nacional de Pediatr\u00eda","place":["Mexico City, Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2675","DOI":"10.3390\/cells9122675","article-title":"CHEK2 germline variants in cancer predisposition: stalemate rather than checkmate","volume":"9","author":"Stolarova","year":"2020","journal-title":"Cells"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-025-02635-1","article-title":"Predisposition to hematopoietic Malignancies by deleterious germline CHEK2 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