Actionable Genes and Carcinogenic Pathways for Gastric Cancer in Latinos.

Area of Science:

• Genomics and Oncology
• Cancer Research
• Population Genetics

Background:

• Gastric cancer (GC) is a leading cause of cancer death globally and a significant health concern among Hispanics in Puerto Rico (PRH).
• The genetic mutational landscape of GC in PRH has not been previously explored, hindering the development of targeted treatment strategies for this population.
• Identifying prevalent genetic alterations is essential for understanding GC progression and improving patient survival in PRH.

Purpose of the Study:

• To identify the most frequent genetic alterations in gastric cancer (GC) tumors from Puerto Rican Hispanics (PRH).
• To compare the genetic mutational profiles of GC in PRH with those of non-Hispanic cohorts.
• To understand the implications of these genetic differences for tumor biology and potential treatment strategies in PRH.

Main Methods:

• Analysis of tumor mutational profiles from 106 PRH GC cases (2015-2022).
• Next-generation sequencing data utilized for 85 cases, categorized into hypermutated and non-hypermutated groups.
• Comparison of mutation frequencies with The Cancer Genome Atlas (TCGA) cohort.

Main Results:

• In non-hypermutated GC, the most common mutations in PRH were TP53 (56.9%), CDH1 (29.2%), ARID1A (27.4%), and KMT2D (25.7%).
• PRH exhibited significantly higher mutation frequencies in key driver genes compared to TCGA.
• Intestinal-type GC in PRH showed higher TP53 mutations, while diffuse-type GC had increased CDH1 mutations.

Conclusions:

• The unique genetic profile of GC in PRH suggests potentially more aggressive tumor biology and poorer prognosis.
• Intestinal-type GC aligns with chromosomal instability (CIN), while diffuse-type GC aligns with genomically stable (GS) classifications, with distinct driver mutations.
• Incorporating Hispanic populations into genomic studies is vital for a comprehensive understanding of GC risk, progression, and for developing effective, personalized therapies.