Nicholas T Gimbrone1, Bhaswati Sarcar1, Edna R Gordian2, Jason I Rivera1, Christian Lopez2, Sean J Yoder3, Jamie K Teer4, Eric A Welsh4, Alberto A Chiappori5, Matthew B Schabath6, Gary W Reuther1, Julie Dutil7, Miosotis Garcia8, Ronald Ventosilla-Villanueva9, Luis Vera-Valdivia10, Alejandro Yabar-Berrocal11, Rodrigo Motta-Guerrero12, Pedro G Santiago-Cardona7, Teresita Muñoz-Antonia2, W Douglas Cress13. 1. Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. 2. Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. 3. Molecular Genomics Core Facility, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. 4. Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. 5. Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. 6. Cancer Epidemiology Programs, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. 7. Basic Sciences Department, Biochemistry and Cancer Biology Divisions, Ponce Health Sciences University, Ponce, Puerto Rico. 8. Endocrinology Department, Central University of the Caribbean, 9 San Juan Municipal Hospital, San Juan, Puerto Rico. 9. Peruvian Cayetano Heredia University, Daniel Alcides Carrión Hospital, Lima, Perú. 10. Edgardo Rebagliati Martins Essalud National Hospital, Lima, Perú. 11. Pathology Department, Rebagliati Martins Essalud National Hospital, Lima, Perú. 12. Peruvian Cayetano Heredia University, Cayetano Heredia National Hospital, Lima, Perú. 13. Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. Electronic address: douglas.cress@moffitt.org.
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 H/L 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, serine/threonine kinase 11 gene [STK11], and tumor protein p53 gene [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 correlated with ancestry, sex, smoking status, and tumor histologic type. RESULTS: Of the adenocarcinomas in the H/L cohort (n = 120), 31% had EGFR mutations, versus 17% in the NHW control group (p < 0.001). KRAS (20% versus 38% [p = 0.002]) and STK11 (8% versus 16% [p = 0.065]) mutations occurred at lower frequency, and mutations in TP53 occurred at similar frequency (46% versus 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 have influenced the rate of EGFR, KRAS, and STK11 mutations. CONCLUSIONS: Driver mutations in H/L patients with lung adenocarcinoma differ in frequency from those in NHW patients associated with their indigenous American ancestry. The spectrum of driver mutations needs to be further assessed in the H/L population.
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 H/L 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, serine/threonine kinase 11 gene [STK11], and tumor protein p53 gene [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 correlated with ancestry, sex, smoking status, and tumor histologic type. RESULTS: Of the adenocarcinomas in the H/L cohort (n = 120), 31% had EGFR mutations, versus 17% in the NHW control group (p < 0.001). KRAS (20% versus 38% [p = 0.002]) and STK11 (8% versus 16% [p = 0.065]) mutations occurred at lower frequency, and mutations in TP53 occurred at similar frequency (46% versus 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 have influenced the rate of EGFR, KRAS, and STK11 mutations. CONCLUSIONS: Driver mutations in H/L patients with lung adenocarcinoma differ in frequency from those in NHW patients associated with their indigenous American ancestry. The spectrum of driver mutations needs to be further assessed in the H/L population.
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