Somatic Mutations and Ancestry Markers in Hispanic Lung Cancer Patients

Abstract

INTRODUCTION To address the lack of genomic data from Hispanic/Latino (H/L) patients with lung cancer, the Latino Lung Cancer Registry was established to collect patient data and biospecimens from these patients. METHODS This retrospective observational study examined lung cancer tumor samples from 163 H/L patients, and tumor-derived DNA was subjected to targeted-exome sequencing (>1000 genes, including EGFR, KRAS, STK11, and TP53) and ancestry analysis. Mutation frequencies in this H/L cohort were compared with those in a similar cohort of non-Hispanic white (NHW) patients and were correlated with ancestry, sex, smoking status, and tumor histology. RESULTS Among adenocarcinomas (n=120) in the H/L cohort, 31% had EGFR mutations, versus 17% in the NHW control group (p < 0.001). KRAS (20% vs. 38%; p=0.002) and STK11 (8% vs. 16%; p=0.065) mutations occurred at lower frequency, and mutations in TP53 occurred at similar frequency (46% vs. 40%; p=0.355) in H/L and NHW patients, respectively. Within the Hispanic cohort, ancestry influenced the rate of TP53 mutations (p=0.009) and may influence the rate of EGFR, KRAS, and STK11 mutations. CONCLUSIONS Driver mutations in H/L lung adenocarcinoma patients differ in frequency from those in NHWs associated with their Indigenous American ancestry. The spectrum of driver mutations needs to be further assessed in the H/L population.

Lung cancer early detection and health disparities: the intersection of epigenetics and ethnicity

“…Groups of Native American heritage display similar trends (61). Gimbrone et al examined over 1,000 genes and noted that a Hispanic/Latino population of 120 lung adenocarcinoma patients exhibited nearly double the mutational frequency of EGFR but decreased prevalence of KRAS and STK11 mutations, relative to Caucasians (62). Other genes assessed in this study did not exhibit significant discrepancies between ethnically based cohorts.…”

Characterization of epidermal growth factor receptor (EGFR) P848L, an unusual EGFR variant present in lung cancer patients, in a murine Ba/F3 model

“…The P741S mutation (in exon 19) was reported previously as a single mutation in basal cell and breast carcinoma . In our previous study , the P741S variant co‐occurred with T785I variant in the same patient. Since T785I variant transformed Ba/F3 cells while the P741S variant did not, T785I is likely the driver mutation when these two variants coexist.…”

“… N196D and I938M lie outside the EGFR kinase domain. N196D was observed in a carcinoid tumor, and I938M was observed in a squamous, both were from cohort of Hispanic lung cancer patients . …”

“…Not surprisingly, novel mutations are emerging, and among these, the exon 19 L747P and exon 20 C797S mutations are found to impute resistance to gefitinib and osimertinib, respectively . While we can predict the drug sensitivity of the majority of cancer‐associated EGFR variants, there are less common EGFR variants that remain poorly characterized, and thus, their clinical relevance remains unclear. In the present study, we have used a Ba/F3 cell line model to rapidly assess the transforming activity and drug sensitivity of a selected cohort of EGFR variants, and included some that are reported previously and some novel variants from a recently published cohort of Hispanic lung cancer patients .…”

Addressing Underrepresented Populations in Lung Cancer Research: The Hispanic/Latino Lung Cancer Registry Identifies Distinct Mutation Profiles for NSCLC

“…4 The registry is an international/multicenter effort between the University of South Florida, Ponce Health Sciences University of Puerto Rico, and the Universidad Perúana Cayetano Heredia in Peru; it consists of data on 163 Hispanic/Latino individuals with recently diagnosed NSCLC. The authors performed targeted exome sequencing on specimens from these 163 individuals with NSCLC to determine how patient ethnicity may affect NSCLC tumor mutation profiles.…”