Genomic differences of patients with hematologic malignancies in different age groups

Area of Science:

• Hematology
• Oncology
• Genomics

Background:

• Hematologic malignancies represent a significant health burden across all age groups.
• Biological underpinnings and age-specific differences in hematologic cancers are not fully understood.

Purpose of the Study:

• To compare clinical and genomic features of hematologic malignancies in children/young adults (CYAs) versus older adults (OAs).
• To identify age-related disparities in genetic mutations, copy number alterations, and driver gene fusions.
• To provide insights into age-specific personalized treatment strategies.

Main Methods:

• Comparative analysis of clinical data and genomic profiles between CYA and OA patient cohorts.
• Identification of differentially mutated genes (DMGs) and copy number alterations (CNAs) across age groups.
• Investigation of protein-protein interaction networks for identified DMGs.

Main Results:

• Significant clinical disparities observed, including sex, ethnicity, metastasis rates, and tumor subtypes.
• CYA hematologic malignancies generally exhibit lower mutational burden compared to OAs.
• Distinct sets of DMGs were identified, with TP53, TET2, and DNMT3A mutated less in CYAs, while NRAS, KRAS, and others were more common in CYAs. CYA malignancies showed more copy number alterations and driver gene fusions.
• Differential CNAs were noted for ARID1B, MYB, TP53, and ESR1 between CYAs and OAs.

Conclusions:

• Hematologic malignancies display substantial age-related clinical and genomic differences.
• Identification of specific genetic alterations in CYAs and OAs provides a basis for age-tailored therapies.
• Comparative genomic analysis reveals critical insights for developing personalized treatment approaches for different age groups.