Integrated analysis of genes encoding ATP‐dependent chromatin remodellers identifies <i>CHD7</i> as a potential target for colorectal cancer therapy

Zhang, Xingyan; Zhou, Yaoyao; Shi, Zhenyu; Liu, Zhongfan; Chen, Hao; Wang, Xiaochen; Cheng, Yiming; Xi, Lishan; Li, Xuanyuan; Zhang, Chunze; Bao, Li; Xuan, Chenghao

doi:10.1002/ctm2.953

Cited by 3 publications

(1 citation statement)

References 44 publications

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“…Additionally, a number of the epigenetic regulators specific to African tumors have been identified as potential therapeutic targets. Chromatin remodeler CHD7 , a somatic driver candidate in colorectal cancer (CRC), promotes CRC cell growth by binding target gene promoters, encouraging an open chromatin conformation and subsequent transcription, whereas CHD7 knockdown inhibits CRC cell growth [ 74 ]. Similarly, POLR1B knockdown induces lung cancer cell apoptosis [ 75 ], VPS72 knockdown inhibits the proliferation, invasion, and migration of hepatocellular carcinoma (HCC) cells [ 76 ], and UBTF silencing suppresses melanoma cell proliferation [ 77 ].…”

Section: Discussionmentioning

confidence: 99%

Alterations in the Epigenetic Machinery Associated with Prostate Cancer Health Disparities

Craddock

Jiang

Patrick

et al. 2023

Cancers

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Prostate cancer is driven by acquired genetic alterations, including those impacting the epigenetic machinery. With African ancestry as a significant risk factor for aggressive disease, we hypothesize that dysregulation among the roughly 656 epigenetic genes may contribute to prostate cancer health disparities. Investigating prostate tumor genomic data from 109 men of southern African and 56 men of European Australian ancestry, we found that African-derived tumors present with a longer tail of epigenetic driver gene candidates (72 versus 10). Biased towards African-specific drivers (63 versus 9 shared), many are novel to prostate cancer (18/63), including several putative therapeutic targets (CHD7, DPF3, POLR1B, SETD1B, UBTF, and VPS72). Through clustering of all variant types and copy number alterations, we describe two epigenetic PCa taxonomies capable of differentiating patients by ancestry and predicted clinical outcomes. We identified the top genes in African- and European-derived tumors representing a multifunctional “generic machinery”, the alteration of which may be instrumental in epigenetic dysregulation and prostate tumorigenesis. In conclusion, numerous somatic alterations in the epigenetic machinery drive prostate carcinogenesis, but African-derived tumors appear to achieve this state with greater diversity among such alterations. The greater novelty observed in African-derived tumors illustrates the significant clinical benefit to be derived from a much needed African-tailored approach to prostate cancer healthcare aimed at reducing prostate cancer health disparities.

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Section: Discussionmentioning

confidence: 99%

Alterations in the Epigenetic Machinery Associated with Prostate Cancer Health Disparities

Craddock

Jiang

Patrick

et al. 2023

Cancers

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Characteristic changes in the mRNA expression profile of plasma exosomes from patients with MPO-ANCA-associated vasculitis and its possible correlations with pathogenesis

Chen,

Zhou,

Qian

et al. 2024

Clin Exp Med

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Alterations in the Epigenetic Machinery Associated With Prostate Cancer Health Disparities

Craddock¹,

Jiang²,

Patrick³

et al. 2023

Preprint

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Prostate cancer is driven by acquired genetic alterations, including those impacting the epigenetic machinery. With African ancestry a significant risk factor for aggressive disease, we hypothesize that dysregulation among the roughly 656 epigenetic genes may contribute to prostate cancer health disparities. Interrogating prostate tumor genomic data from 109 men of southern African and 56 men of European Australian ancestry, we found African-derived tumors to present with a longer tail of epigenetic driver gene candidates (72 versus 10). Biased towards African-specific drivers (63 versus 9 shared), many are novel to prostate cancer (18/63) including several putative therapeutic targets (CHD7, DPF3, POLR1B, SETD1B, UBTF and VPS72). Through clustering of all variant types and copy number alterations, we describe two epigenetic PCa taxonomies capable of differentiating patients by ancestry and predicted clinical outcomes. We identified top genes in African and European-derived tumors that represent a multifunctional “generic machinery”, alteration to which may be instrumental in epigenetic dysregulation and prostate tumorigenesis. In conclusion, numerous somatic alterations in the epigenetic machinery drive prostate carcinogenesis but African-derived tumors appear to achieve this with greater diversity amongst such alterations. The greater novelty observed in African-derived tumors illustrates the significant clinical benefit to be derived from a much needed African tailored approach to prostate cancer healthcare aimed at reducing prostate cancer health disparities.

show abstract

Integrated analysis of genes encoding ATP‐dependent chromatin remodellers identifies CHD7 as a potential target for colorectal cancer therapy

Cited by 3 publications

References 44 publications

Alterations in the Epigenetic Machinery Associated with Prostate Cancer Health Disparities

Alterations in the Epigenetic Machinery Associated with Prostate Cancer Health Disparities

Characteristic changes in the mRNA expression profile of plasma exosomes from patients with MPO-ANCA-associated vasculitis and its possible correlations with pathogenesis

Alterations in the Epigenetic Machinery Associated With Prostate Cancer Health Disparities

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