Kiatprungvech Nattaradee, Sangkum Premsant, Malinee Rozita, Sommaluan Suchada, Korkiatsakul Veerawat, Worawichawong Suchin, Rerkamnuaychoke Budsaba, Kongruang Adcharee, Aeesoa Suraida, Lertsithichai Panuwat, Kijvikai Kittinut, Kongchareonsombat Wisoot, Siriboonpiputtana Teerapong
Division of Urology, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Pract Lab Med. 2024 May 25;40:e00410. doi: 10.1016/j.plabm.2024.e00410. eCollection 2024 May.
While recent studies have demonstrated several genetic alterations are associated with pathogenesis of RCC, the significance of cyclin-dependent kinase inhibitor 2A and cyclin-dependent kinase inhibitor 2B in tumorigenesis of RCC is less clear. We investigate the distribution of and mutations in patients with RCC and analyze the impact of and mutations on RCC.
A pathological examination was conducted using thirty fresh renal tissue samples with renal masses that had undergone partial or radical nephrectomy. Multiplex ligation-dependent probe amplification (MLPA) was used to detect genetic aberrations of and in genomic DNA isolated from samples. Subsequently, and mutations were confirmed using chromosomal microarray technique.
Twenty-one patients were diagnosed with RCC, eight with benign diseases, including angiomyolipoma (AML) and oncocytoma, and one with mucinous adenocarcinoma of renal pelvis. Two of twenty-one patients (9.5 %) with clear-cell RCC were positive for and gene deletions. Interestingly, patients with and mutations were associated with sarcomatoid patterns of RCC (2 out of 4, 50 %). In contrast, no or deletions were detected in samples from benign renal tumors, papillary RCC, or other kidney cancers.
This study demonstrated the potential use of and as biomarkers for the prognostic and molecular classification of renal cancer. and mutations may be associated with RCC development and sarcomatoid changes. Further research is needed to understand the underlying molecular mechanisms of and in the pathogenesis of RCC.
虽然最近的研究表明几种基因改变与肾细胞癌（RCC）的发病机制相关，但细胞周期蛋白依赖性激酶抑制剂2A（CDKN2A）和细胞周期蛋白依赖性激酶抑制剂2B（CDKN2B）在RCC肿瘤发生中的意义尚不清楚。我们调查了RCC患者中CDKN2A和CDKN2B的突变分布，并分析了CDKN2A和CDKN2B突变对RCC的影响。
对30例接受了部分或根治性肾切除术的有肾肿块的新鲜肾组织样本进行病理检查。使用多重连接依赖探针扩增（MLPA）检测从样本中分离的基因组DNA中CDKN2A和CDKN2B的基因畸变。随后，使用染色体微阵列技术确认CDKN2A和CDKN2B突变。
21例患者被诊断为RCC，8例患有良性疾病，包括血管平滑肌脂肪瘤（AML）和嗜酸细胞瘤，1例患有肾盂黏液腺癌。21例透明细胞RCC患者中有2例（9.5%）CDKN2A和CDKN2B基因缺失呈阳性。有趣的是，CDKN2A和CDKN2B突变的患者与RCC的肉瘤样模式相关（4例中有2例，50%）。相比之下，在良性肾肿瘤、乳头状RCC或其他肾癌的样本中未检测到CDKN2A或CDKN2B缺失。
本研究证明了CDKN2A和CDKN2B作为肾癌预后和分子分类生物标志物的潜在用途。CDKN2A和CDKN2B突变可能与RCC的发展和肉瘤样改变有关。需要进一步研究以了解CDKN2A和CDKN2B在RCC发病机制中的潜在分子机制。
