使用Oncomine结肠cfDNA检测法检测前驱病变和结直肠癌的血浆突变谱。

Plasma mutation profile of precursor lesions and colorectal cancer using the Oncomine Colon cfDNA Assay.

作者信息

Dos Reis Mariana Bisarro, Dos Santos Wellington, de Carvalho Ana Carolina, Lima Adhara Brandão, Reis Monise Tadin, Santos Florinda, Reis Rui Manuel, Guimarães Denise Peixoto

机构信息

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.

Department of Pathology, Barretos Cancer Hospital, Barretos, SP, Brazil.

出版信息

BMC Cancer. 2024 Dec 18;24(1):1547. doi: 10.1186/s12885-024-13287-2.

DOI:10.1186/s12885-024-13287-2

PMID:39695441

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11657448/

Abstract

BACKGROUND

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Early detection of precursor lesions or early-stage cancer could hamper cancer development or improve survival rates. Liquid biopsy, which detects tumor biomarkers, such as mutations, in blood, is a promising avenue for cancer screening.

AIM

To assess the presence of genetic variants in plasma cell-free tumor DNA from patients with precursor lesions and colorectal cancer using the commercial Oncomine Colon cfDNA Assay.

MATERIAL AND METHODS

Cell-free DNA (cfDNA) samples from the plasma of 52 Brazilian patients were analyzed. Eight patients did not have any significant lesions (five normal colonoscopies and three hyperplastic polyps), 24 exhibited precursor lesions (13 nonadvanced adenomas, 10 advanced adenomas, and one sessile serrated lesion), and 20 patients with cancer (CRC). The mutation profile of 14 CRC-associated genes were determined by next-generation sequencing (NGS) using the Oncomine Colon cfDNA Assay in the Ion Torrent PGM/S5 sequencer.

RESULTS

Thirty-three variants were detected in eight genes (TP53, PIK3CA, FBXW7, APC, BRAF, GNAS, KRAS, and SMAD4). No variants were detected in the AKT1, CTNNB1, EGFR, ERBB2, MAP2K1 and NRAS genes. All variants were considered pathogenic and classified as missense or truncating. The TP53 gene harbored the most variants (48.48%), followed by the KRAS gene (15.15%) and the APC gene (9.09%). It was possible to detect the presence of at least one pathogenic variant in cfDNA in 60% of CRC patients (12/20) and 25% of precursor lesions (6/24), which included variants in three patients with nonadvanced adenoma (3/13 - 23.08%) and three with advanced adenomas (3/10 - 30%). No variants were detected in the eight patients with normal findings during colonoscopy. The detection of mutations showed a sensitivity of 60% and a specificity of 100% for detecting CRC and a sensitivity of 50% and a specificity of 100% for detecting advanced lesions.

CONCLUSION

The detection of plasma NGS-identified mutations could assist in early screening and diagnostic of CRC in a noninvasive manner.

摘要

背景

结直肠癌（CRC）是全球癌症死亡的第二大主要原因。早期检测前驱病变或早期癌症可阻碍癌症发展或提高生存率。液体活检是一种很有前景的癌症筛查途径，它可以检测血液中的肿瘤生物标志物，如突变。

目的

使用商业的Oncomine结肠游离DNA检测法评估前驱病变患者和结直肠癌患者血浆游离肿瘤DNA中基因变异的存在情况。

材料与方法

分析了52名巴西患者血浆中的游离DNA（cfDNA）样本。8名患者没有任何显著病变（5例结肠镜检查正常，3例增生性息肉），24名患者有前驱病变（13例非进展性腺瘤、10例进展性腺瘤和1例无蒂锯齿状病变），20名患者患有癌症（CRC）。使用Ion Torrent PGM/S5测序仪上的Oncomine结肠cfDNA检测法，通过下一代测序（NGS）确定14个CRC相关基因的突变谱。

结果

在8个基因（TP53、PIK3CA、FBXW7、APC、BRAF、GNAS、KRAS和SMAD4）中检测到33个变异。在AKT1、CTNNB1、EGFR、ERBB2、MAP2K1和NRAS基因中未检测到变异。所有变异均被认为是致病性的，分类为错义或截短突变。TP53基因变异最多（48.48%），其次是KRAS基因（15.15%）和APC基因（9.09%）。在60%的CRC患者（12/20）和25%的前驱病变患者（6/24）中，能够检测到cfDNA中至少存在一种致病性变异，其中包括3例非进展性腺瘤患者（3/13 - 23.08%）和3例进展性腺瘤患者（3/10 - 30%）。在结肠镜检查结果正常的8名患者中未检测到变异。检测突变对CRC的检测灵敏度为60%，特异性为100%；对进展性病变的检测灵敏度为50%，特异性为100%。