Shaheenah Dawood, Nippun Sandhir, Marwan Akasheh, Maroun El Khoury, Sonia Otsmane, Muath Alnassar, Omalkhair Abulkhair, Fadi Farhat, Steve Olsen
{"title":"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。","authors":"Shaheenah Dawood, Nippun Sandhir, Marwan Akasheh, Maroun El Khoury, Sonia Otsmane, Muath Alnassar, Omalkhair Abulkhair, Fadi Farhat, Steve Olsen","doi":"10.1159/000541571","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genomic Landscape of Advanced Solid Tumors in Middle East and North Africa Using Circulating Tumor DNA in Routine Clinical Practice.\",\"authors\":\"Shaheenah Dawood, Nippun Sandhir, Marwan Akasheh, Maroun El Khoury, Sonia Otsmane, Muath Alnassar, Omalkhair Abulkhair, Fadi Farhat, Steve Olsen\",\"doi\":\"10.1159/000541571\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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. 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Genomic Landscape of Advanced Solid Tumors in Middle East and North Africa Using Circulating Tumor DNA in Routine Clinical Practice.
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.
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.
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