Department of Pathology, Aydın Adnan Menderes University Faculty of Medicine, Aydın, Turkey.
Turk J Gastroenterol. 2023 Nov;34(11):1124-1133. doi: 10.5152/tjg.2023.22682.
BACKGROUND/AIMS: Recent studies that reveal the molecular profiles of colorectal carcinomas have demonstrated tumor heterogeneity. Characterization of colorectal carcinoma-specific genomic alterations is essential for developing more successful and targeted treat- ment protocols. Moreover, it is vital in elucidating the pathogenesis and mechanisms of resistance against treatment and predicting prognosis.
The study included 73 cases diagnosed with colorectal carcinomas and subjected to molecular analysis by the next-generation sequencing. The association between the clinicopathologic parameters and pathogenic mutations detected in 32 genes was evaluated.
Pathogenic mutations were determined in a total of 24 genes. The Cell Division Cycle 27 (CDC27), Kirsten rat sarcoma viral proto-oncogene (KRAS), serine/threonine protein kinase B-raf (BRAF), phosphatase and tensin homolog, breast cancer 2 (BRCA2), and phosphotidylinositol-4,5-biphosphate 3-kinase (PIK3CA) mutations were determined at higher rates, with the adenomatous polypo- sis coli mutation determined at a lower rate than in the literature. There were significant positive correlations between CDC27 and phosphatase and tensin homolog (PTEN), PTEN and BRCA2, and PTEN and adenomatous polyposis coli (APC) concomitant muta- tions, whereas negative correlations were present between BRAF and KRAS. Statistically significant relationships were present between KRAS exon 2 and mucinous morphology, PIK3CA and absence of perineural invasion, BRAF and tumor differentiation/localization, MutS homolog 3 (MSH3) and tumor diameter, and BRCA2 and absence of lymph node metastasis.
It is necessary to have a comprehensive database of genomic alterations of colorectal carcinomas to interpret mutations more accurately clinically. There are no studies on the frequency of mutations in colorectal carcinomas in the Turkish population; thus, follow-up and treatment protocols are organized following the European and American databases and guidelines. A comprehensive study of the colorectal carcinoma patients' mutation profile in the Turkish patient cohort by the next-generation sequencing method will help to provide significant therapeutic, prognostic, and predictive data and design more successful treatment and follow-up strategies.
背景/目的：最近揭示结直肠癌分子谱的研究表明肿瘤存在异质性。对结直肠癌特异性基因组改变进行特征描述对于开发更成功和靶向的治疗方案至关重要。此外，这对于阐明治疗耐药的发病机制和机制以及预测预后也很重要。
该研究纳入了 73 例经分子分析诊断为结直肠癌的病例，并通过下一代测序进行了分析。评估了 32 个基因中检测到的临床病理参数与致病突变之间的关系。
总共确定了 24 个基因的致病突变。细胞分裂周期蛋白 27（CDC27）、Kirsten 大鼠肉瘤病毒原癌基因（KRAS）、丝氨酸/苏氨酸蛋白激酶 B-raf（BRAF）、磷酸酶和张力蛋白同源物，乳腺癌 2（BRCA2）和磷酸肌醇-4,5-二磷酸 3-激酶（PIK3CA）突变的发生率较高，而腺瘤性息肉突变的发生率低于文献报道。CDC27 与磷酸酶和张力蛋白同源物（PTEN）、PTEN 与 BRCA2 以及 PTEN 与腺瘤性息肉（APC）同时突变之间存在显著的正相关，而 BRAF 与 KRAS 之间存在负相关。KRAS 外显子 2 与黏液形态、PIK3CA 与无神经周围侵犯、BRAF 与肿瘤分化/定位、MutS 同源物 3（MSH3）与肿瘤直径以及 BRCA2 与无淋巴结转移之间存在统计学显著关系。
为了更准确地进行临床解读，需要建立结直肠癌基因组改变的综合数据库。土耳其人群结直肠癌突变的频率尚无研究；因此，根据欧洲和美国的数据库和指南制定了随访和治疗方案。通过下一代测序方法对土耳其患者队列中结直肠癌患者的突变谱进行全面研究，将有助于提供有意义的治疗、预后和预测数据，并设计更成功的治疗和随访策略。
