Baylor College of Medicine Cancer Center-Cancer Center Support Grant

卡波西肉瘤（KS）是迄今为止与人类疱疹病毒-8 (HHV-8)/KS相关疱疹病毒（KSHV）感染相关的最常见的恶性肿瘤，是撒哈拉以南非洲地区最常见的儿童癌症之一。在过去的十年里，我们在德克萨斯州儿童医院的贝勒国际儿童艾滋病倡议/马拉维利隆圭的全球希望（血液肿瘤学儿科卓越）临床卓越中心的儿童艾滋病恶性项目已经照顾了200多名患有KS的儿童。我们的工作强调了儿童KS不同于成人疾病的临床特征，定义了儿科疾病表现的异质性，并建立了风险分层治疗方案，提高了长期生存率。长期完全缓解和无事件生存可以实现，特别是在儿童淋巴结性KS。与此形成鲜明对比的是，晚期内脏或播散性疾病的患者，尽管采用了强化化疗方法，但死亡率仍然很高。我们还确定了临床亚组与kshv介导的儿童疾病特异性KS肿瘤发生机制之间的关联。然而，对KS的内在致病机制的认识仍存在空白。该研究旨在通过对马拉维利隆圭（Lilongwe）最大的现有儿童KS患者生物队列（n=70）的肿瘤标本进行分析，确定儿童KS的体细胞遗传改变，并确定其与临床和病毒学特征的相关性。通过对儿童KS分子特征的进一步了解，我们的目标是发现生物标志物和可靶向通路，从而为开发新的诊断、预后和治疗策略提供信息。

Kaposi sarcoma (KS) is by far the most common malignancy associated with human herpesvirus-8 (HHV-8)/KS-associated herpesvirus (KSHV) infection and ranks among the most common overall childhood cancers in sub-Saharan Africa. Over the past decade, our pediatric HIV malignancy program at the Baylor International Pediatric AIDS Initiative at Texas Children's Hospital/Global HOPE (Hematology-Oncology Pediatric Excellence) Clinical Center of Excellence in Lilongwe, Malawi has cared for over 200 children with KS. Our work has highlighted the clinical characteristics that render childhood KS distinct from adult disease, defined the heterogeneity in disease presentation specific to pediatrics, and established risk-stratified treatment regimens that have improved long-term survival. Long-term complete remission and event-free survival can be achieved, especially in children with lymphadenopathic KS. In stark contrast, patients with advanced visceral or disseminated disease experience high mortality rates despite intensified chemotherapeutic approaches. We have also identified associations between clinical sub-groups and KSHV-mediated mechanisms of KS oncogenesis specific to childhood disease. However, there remains a gap in knowledge concerning the inherent pathogenic mechanisms of KS. The proposed study seeks to define somatic genetic alterations of pediatric KS and determine correlations with clinical and virologic features through analysis of tumor specimens from the largest existing biocohort of childhood KS patients (n=70) from Lilongwe, Malawi. Through improved understanding of the molecular features of pediatric KS, we aim to discover biomarkers and targetable pathways that may inform the development of novel diagnostic, prognostic and therapeutic strategies.