The Genomic Landscape of a Restricted ALL Cohort from Patients Residing on the U.S./Mexico Border

• Main Authors: Alice Hernandez Grant, Yoshira Marie Ayala-Marin, Jonathon Edward Mohl, Elisa Robles-Escajeda, Georgialina Rodriguez, Julie Dutil, Robert Arthur Kirken
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: International Journal of Environmental Research and Public Health
• Subjects: ALL; relapse; precision medicine; Hispanic health disparities; <i>KRAS</i>; <i>STAT5B</i>
• Online Access: https://www.mdpi.com/1660-4601/18/14/7345

Next-generation sequencing (NGS) has identified unique biomarkers yielding new strategies in precision medicine for the treatment of Acute lymphoblastic leukemia (ALL). Hispanics show marked health disparities in ALL, often absent in clinical trials or cancer research. Thus, it is unknown whether Hispanics would benefit equally from curated data currently guiding precision oncology. Using whole-exome sequencing, nine ALL patients were screened for mutations within genes known to possess diagnostic, prognostic and therapeutic value. Genes mutated in Hispanic ALL patients from the borderland were mined for potentially pathogenic variants within clinically relevant genes. <i>KRAS</i> G12A was detected in this unique cohort and its frequency in Hispanics from the TARGET-ALL Phase II database was three-fold greater than that of non-Hispanics. <i>STAT5B</i> N642H was also detected with low frequency in Hispanic and non-Hispanic individuals within TARGET. Its detection within this small cohort may reflect a common event in this demographic. Such variants occurring in the MAPK and JAK/STAT pathways may be contributing to Hispanic health disparities in ALL. Notable variants in <i>ROS1</i>, <i>WT1</i>, and <i>NOTCH2</i> were observed in the ALL borderland cohort, with <i>NOTCH2</i> C19W occurring most frequently. Further investigations on the pathogenicity of these variants are needed to assess their relevance in ALL.