Genomic Landscape of Advanced Solid Tumors in Middle East and North Africa Using Circulating Tumor DNA in Routine Clinical Practice.

IF 2.5 3区医学 Q3 ONCOLOGY Oncology Pub Date : 2024-09-27 DOI:10.1159/000541571

Shaheenah Dawood, Nippun Sandhir, Marwan Akasheh, Maroun El Khoury, Sonia Otsmane, Muath Alnassar, Omalkhair Abulkhair, Fadi Farhat, Steve Olsen

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引用次数: 0

Abstract

Introduction: Next-generation sequencing (NGS) of tumor DNA can detect actionable drivers and help guide therapy for patients with advanced-stage cancers. While tissue-based genotyping is considered a standard of care, blood-based genotyping is emerging as a valid alternative. Tumor genomic profiles may vary by region, and data from the Middle East and North Africa (MENA) are not widely available. This study elucidates the genomic landscape of advanced solid cancers in patients from the MENA region by retrospectively analyzing results from NGS circulating tumor DNA (ctDNA) testing.

Methods: In routine clinical practice, 926 plasma samples from 767 patients with advanced cancers from the MENA region were profiled using a comprehensive NGS assay (Guardant360®). We conducted a pan-cancer analysis and sub-analyses focusing on lung, breast, and colorectal cancers.

Results: In the pan-cancer group, TP53 (58.5%), EGFR (20.4%), and KRAS (18.9%) were the most frequently mutated genes. EGFR (10.2%), FGFR1 (4.9%), and PIK3CA (4.9%) showed the most amplifications, while fusions were observed in 2.7% of patients, including ALK, FGFR2, and RET. For lung adenocarcinoma, EGFR (30.5%), KRAS (19.3%), and ERBB2 (4.6%) were the most frequently identified alterations among the genes recommended for evaluation by the National Comprehensive Cancer Network (NCCN). In patients with breast cancer, PIK3CA (35.3%), ESR1 (21.7%), and BRCA1/2 (13.3%) had the most prevalent alterations among NCCN-recommended genes. In colorectal cancer, KRAS (39.0%), NRAS (8.0%), and BRAF (V600E, 4.0%) were the most observed mutations among genes recommended by the NCCN. Comparing this cohort to publicly available Western and Eastern datasets also indicated similarities (including PIK3CA in breast cancer) and variances (including EGFR in lung adenocarcinoma) in key genes of interest in the analyzed cancer types.

Conclusion: Overall, our findings provide insight into the genomic landscape of individuals with advanced solid organ malignancies from the MENA region and support the role of ctDNA in guiding therapeutic decisions.

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利用常规临床实践中的循环肿瘤 DNA (ctDNA)，分析中东和北非晚期实体瘤的基因组状况。

简介肿瘤 DNA 的下一代测序（NGS）可检测可采取行动的驱动因素，并帮助指导晚期癌症患者的治疗。基于组织的基因分型被认为是标准的治疗方法，而基于血液的基因分型正在成为一种有效的替代方法。肿瘤基因组图谱可能因地区而异，中东和北非（MENA）的数据并不广泛。本研究通过回顾性分析 NGS ctDNA 检测结果，阐明了中东和北非地区晚期实体瘤患者的基因组情况：在常规临床实践中，我们使用一种全面的 NGS 检测方法 (Guardant360®) 分析了来自中东和北非地区 767 名晚期癌症患者的 926 份血浆样本。我们进行了一项泛癌症分析和侧重于肺癌、乳腺癌和结直肠癌的子分析：在泛癌症组中，TP53（58.5%）、表皮生长因子受体（20.4%）和 KRAS（18.9%）是最常见的突变基因。表皮生长因子受体（10.2%）、表皮生长因子受体1（4.9%）和PIK3CA（4.9%）扩增最多，而2.7%的患者出现融合，包括ALK、表皮生长因子受体2和RET。在肺腺癌中，表皮生长因子受体（30.5%）、KRAS（19.3%）和ERBB2（4.6%）是美国国家综合癌症网络（NCCN）建议评估的基因中最常发现的改变。在乳腺癌患者中，PIK3CA（35.3%）、ESR1（21.7%）和 BRCA1/2 （13.3%）是 NCCN 推荐基因中最常见的改变。在结直肠癌中，KRAS（39.0%）、NRAS（8.0%）和BRAF（V600E，4.0%）是NCCN推荐基因中观察到的最常见突变。将该队列与公开的西方和东方数据集进行比较还表明，在所分析的癌症类型中，关键相关基因存在相似性（包括乳腺癌中的 PIK3CA）和差异性（包括肺腺癌中的表皮生长因子受体）：总之，我们的研究结果让人们深入了解了中东和北非地区晚期实体器官恶性肿瘤患者的基因组情况，并支持 ctDNA 在指导治疗决策中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncology 医学-肿瘤学

CiteScore

6.00

自引率

2.90%

发文量

审稿时长

6-12 weeks

期刊介绍： Although laboratory and clinical cancer research need to be closely linked, observations at the basic level often remain removed from medical applications. This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation. The fundamental purpose of this effort is to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease. The journal publishes significant clinical studies from cancer programs around the world, along with important translational laboratory findings, mini-reviews (invited and submitted) and in-depth discussions of evolving and controversial topics in the oncology arena. A unique feature of the journal is a new section which focuses on rapid peer-review and subsequent publication of short reports of phase 1 and phase 2 clinical cancer trials, with a goal of insuring that high-quality clinical cancer research quickly enters the public domain, regardless of the trial’s ultimate conclusions regarding efficacy or toxicity.