宿主核基因组拷贝数变异可识别艾滋病毒感染者的高危肛门前癌。

Host Nuclear Genome Copy Number Variations Identify High-Risk Anal Precancers in People Living With HIV.

机构信息

Division of General Internal Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.

Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.

出版信息

J Acquir Immune Defic Syndr. 2024 Jun 1;96(2):190-195. doi: 10.1097/QAI.0000000000003409.

DOI:10.1097/QAI.0000000000003409

PMID:38630441

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11108747/

Abstract

BACKGROUND

People living with HIV (PLWH) have substantially increased incidence of anal precancer and cancer. There are very little data regarding genomic disturbances in anal precancers among PLWH. In this study, specific chromosomal variants were identified in anal squamous intraepithelial lesions.

METHODS

Overall, 63 anal biopsy specimens (27 low-grade intraepithelial lesions [LSIL] and 36 high-grade intraepithelial lesions [HSIL]) were collected from PLWH obtained as part of anal cancer screening in our NYC-based health system. Data on patient demographics, anal cytological, and high-risk human papillomavirus (HR-HPV) diagnoses were collected. Specimens were tested for a panel of chromosomal alterations associated with HPV-induced oncogenesis using fluorescence in situ hybridization, and analyses compared the associations of these alterations with clinical characteristics.

RESULTS

Gains of 3q26, 5p15, 20q13, and cen7 were detected in 42%, 31%, 31%, and 19% of HSIL compared with 7%, 0%, 4%, and 0% of LSIL, respectively. If at least 1 abnormality was observed, 89% had a 3q26 gain. In lesions with 5p15 gains, 20q13 gains co-occurred in 91% of cases, while cen7 gain only co-occurred with the other 3 alterations. The sensitivity and specificity of any alteration to predict HSIL were 47% (95% CI: 30%-65%) and 93% (95% CI: 76%-99%), respectively.

CONCLUSIONS

Genomic alterations seen in HPV-associated cancers may help distinguish anal LSIL from HSIL. 3q26 amplification may be an early component of anal carcinogenesis, preceding 5p16, 20q13, and/or chr7.

IMPACT

Insights into potential genomic biomarkers for discriminating high-risk anal precancers are shared.

摘要

背景

HIV 感染者（PLWH）肛门癌前病变和癌症的发病率显著增加。关于 PLWH 肛门癌前病变中的基因组紊乱，数据非常少。在这项研究中，我们在肛门鳞状上皮内病变中鉴定了特定的染色体变体。

方法

总体而言，我们从我们的纽约市健康系统中获得的肛门癌筛查中收集了 63 个肛门活检标本（27 个低级别上皮内病变 [LSIL] 和 36 个高级别上皮内病变 [HSIL]）。收集了患者人口统计学、肛门细胞学和高危型人乳头瘤病毒（HR-HPV）诊断的数据。使用荧光原位杂交检测了与 HPV 诱导的致癌作用相关的一组染色体改变的标本，并分析了这些改变与临床特征的关联。

结果

HSIL 中 3q26、5p15、20q13 和 cen7 的增益分别为 42%、31%、31%和 19%，而 LSIL 中分别为 7%、0%、4%和 0%。如果至少观察到 1 种异常，则 89%的患者存在 3q26 增益。在 5p15 增益的病变中，20q13 增益在 91%的病例中共同发生，而 cen7 增益仅与其他 3 种改变共同发生。任何改变预测 HSIL 的敏感性和特异性分别为 47%（95%CI：30%-65%）和 93%（95%CI：76%-99%）。