Comparing Genomic Profiles of ALK Fusion-Positive and ALK Fusion-Negative Nonsmall Cell Lung Cancer Patients.

IF 1.2 Q4 GENETICS & HEREDITY
Global Medical Genetics Pub Date : 2024-06-13 eCollection Date: 2024-06-01 DOI:10.1055/s-0044-1787301
Wenchao Xia, Jing Yang, Hongbin Li, Ling Li, Jinfeng Liu
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引用次数: 0

Abstract

Background  Anaplastic lymphoma kinase ( ALK ) fusion events account for 3 to 7% of genetic alterations in patients with nonsmall cell lung cancer (NSCLC). This study aimed to explore the landscape of ALK fusion-positive and ALK fusion-negative in a large cohort of NSCLC patients. Methods  The formalin-fixed paraffin-embedded specimens of NSCLC patients who underwent next-generation sequencing from 2020 to 2023 in Yinfeng Gene Technology Co., Ltd. Clinical laboratory were included in this study. Results  In the current study, a total of 180 (3.20%) patients tested positive for ALK fusions in 5,622 NSCLC samples. Within the ALK -positive cohort, a total of 228 ALK fusions were identified. Furthermore, five novel ALK fusion partners, including DAB1-ALK , KCMF1-ALK , KIF13A-ALK , LOC643770-ALK , and XDH-ALK were identified. In cases with ALK fusion-positive, TP53 alterations were the most prevalent (26.3%), followed by CDKN2A (8.4%), epidermal growth factor receptor ( EGFR , 5.6%), and ALK (5.6%). By contrast, EGFR alterations were most prevalent (51%) in patients with ALK fusion-negative NSCLC, followed by TP53 (42.7%), KRAS (11.6%), and CDKN2A (11.3%). A total of 10 cases where ALK fusion co-occurred with EGFR mutations were also identified. Notably, the ALK fusion positivity rate was higher in younger patients ( p  < 0.0001) and in female patients ( p  = 0.0429). Additionally, positive ALK test results were more prevalent in patients with high programmed death-ligand 1 expression, especially when applying a 50% cutoff. Conclusions  Collectively, these findings offer valuable genomic insights that could inform the personalized clinical care of patients with NSCLC harboring ALK fusions within the context of precision medicine.

比较 ALK 融合阳性和 ALK 融合阴性非小细胞肺癌患者的基因组特征
背景 在非小细胞肺癌(NSCLC)患者中,无性淋巴瘤激酶(ALK)融合事件占基因改变的3%至7%。本研究旨在探索一大批 NSCLC 患者中 ALK 融合阳性和 ALK 融合阴性的情况。方法 将 2020 年至 2023 年期间在银丰基因技术有限公司临床实验室进行新一代测序的 NSCLC 患者的福尔马林固定石蜡包埋标本纳入本研究。本研究纳入了在银丰基因技术有限公司临床实验室进行新一代测序的 2020 年至 2023 年 NSCLC 患者石蜡包埋标本。结果 在本次研究中,5622 份 NSCLC 样本中共有 180 例(3.20%)患者检测出 ALK 融合阳性。在ALK阳性组群中,共鉴定出228例ALK融合。此外,还发现了五种新的ALK融合伙伴,包括DAB1-ALK、KCMF1-ALK、KIF13A-ALK、LOC643770-ALK和XDH-ALK。在ALK融合阳性病例中,TP53改变最普遍(26.3%),其次是CDKN2A(8.4%)、表皮生长因子受体(EGFR,5.6%)和ALK(5.6%)。相比之下,在ALK融合阴性的NSCLC患者中,表皮生长因子受体的改变最为普遍(51%),其次是TP53(42.7%)、KRAS(11.6%)和CDKN2A(11.3%)。此外,还发现了10例ALK融合与表皮生长因子受体突变共存的病例。值得注意的是,年轻患者的ALK融合阳性率更高(P P = 0.0429)。此外,ALK检测阳性结果在程序性死亡配体1高表达的患者中更为普遍,尤其是当采用50%的临界值时。结论 总的来说,这些发现提供了宝贵的基因组学见解,可为精准医疗背景下携带 ALK 融合的 NSCLC 患者的个性化临床治疗提供参考。
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来源期刊
Global Medical Genetics
Global Medical Genetics GENETICS & HEREDITY-
自引率
11.80%
发文量
30
审稿时长
14 weeks
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