TY - JOUR
T1 - Amplification of MYC and Its Enhancer Correlates With Genetic Ancestry in Lung Squamous Cell Carcinoma
AU - Jain, Sejal
AU - Bai, Xuechun
AU - Mallick, Samyukta
AU - Kinghorn, Branden
AU - May, Benjamin
AU - Yao, Alexandria G.
AU - Allen-Gipson, Diane
AU - Zhang, Xiaoyang
AU - Henick, Brian S.
AU - Momen-Heravi, Fatemeh
AU - Carrot-Zhang, Jian
AU - Taylor, Alison M.
N1 - Publisher Copyright:
© 2024 by American Society of Clinical Oncology.
PY - 2024/10/1
Y1 - 2024/10/1
N2 - PURPOSE In lung squamous cell carcinoma (LUSC), Black patients show significantly higher incidence and lower overall survival than White patients. Although socioeconomic factors likely contribute to this survival disparity, genomic factors have yet to be elucidated in LUSC. METHODS Using 416 LUSC tumor samples in the Cancer Genome Atlas (TCGA), we assessed genomic and transcriptomic profiles by ancestry. We replicated our analyses in pan-cancer data from TCGA, the American Association of Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (GENIE), and Columbia University Medical Center. RESULTS We found increased MYC amplification, LUSC-specific MYC enhancer amplification, and chromosome arm 8q (chr8q) gain to be significantly associated with genetic AFR (African) ancestry in LUSC in TCGA. Furthermore, expression of MYC target genes was significantly enriched in AFR samples. Local ancestry analysis identified correlation of chr8q gain with AFR ancestry at the MYC locus in TCGA. We also found a significant correlation between chr8q and AFR ancestry in multiple cancer types and pan-cancer in TCGA. Similarly, in a pan-cancer subset of AACR GENIE data, we found a significant correlation between chr8q gain and race. CONCLUSION Together, our data suggest that ancestry may influence amplification of not only MYC but also its enhancer in LUSC. They also suggest a role for genetic ancestry in chr8q aneuploidy in cancer. These studies further define and expand patients who may benefit from future anti-MYC therapeutic approaches.
AB - PURPOSE In lung squamous cell carcinoma (LUSC), Black patients show significantly higher incidence and lower overall survival than White patients. Although socioeconomic factors likely contribute to this survival disparity, genomic factors have yet to be elucidated in LUSC. METHODS Using 416 LUSC tumor samples in the Cancer Genome Atlas (TCGA), we assessed genomic and transcriptomic profiles by ancestry. We replicated our analyses in pan-cancer data from TCGA, the American Association of Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (GENIE), and Columbia University Medical Center. RESULTS We found increased MYC amplification, LUSC-specific MYC enhancer amplification, and chromosome arm 8q (chr8q) gain to be significantly associated with genetic AFR (African) ancestry in LUSC in TCGA. Furthermore, expression of MYC target genes was significantly enriched in AFR samples. Local ancestry analysis identified correlation of chr8q gain with AFR ancestry at the MYC locus in TCGA. We also found a significant correlation between chr8q and AFR ancestry in multiple cancer types and pan-cancer in TCGA. Similarly, in a pan-cancer subset of AACR GENIE data, we found a significant correlation between chr8q gain and race. CONCLUSION Together, our data suggest that ancestry may influence amplification of not only MYC but also its enhancer in LUSC. They also suggest a role for genetic ancestry in chr8q aneuploidy in cancer. These studies further define and expand patients who may benefit from future anti-MYC therapeutic approaches.
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U2 - 10.1200/PO.24.00223
DO - 10.1200/PO.24.00223
M3 - Article
C2 - 39447097
AN - SCOPUS:85208664372
SN - 2473-4284
VL - 8
JO - JCO Precision Oncology
JF - JCO Precision Oncology
M1 - e2400223
ER -