Köhn Linda, Svenson Ulrika, Ljungberg Börje, Roos Göran
*Department of Medical Biosciences/Pathology †Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
Appl Immunohistochem Mol Morphol. 2015 May-Jun;23(5):334-42. doi: 10.1097/PAI.0000000000000087.
Detailed genetic profiling of clear cell renal cell carcinoma (ccRCC) has revealed genomic regions commonly affected by structural changes and a general genetic heterogeneity. VHL and PBRM1, both located at chromosome 3p, are 2 major genes mutated at high frequency but apart from these aberrations, the mutational landscape in ccRCC is largely undefined. Potential prognostic information given by the genomic changes appears to depend on the particular cohort studied. We analyzed a Swedish ccRCC cohort of 74 patients and found common changes (loss or gain occurring in >20% of the tumors) in 12 chromosomal regions (1p, 3p, 3q, 5q, 6q, 7p, 7q 8p, 9p, 9q, 10q, and 14q). A poor outcome was associated with gain of 7q and losses on 9p, 9q, and 14q. These aberrations were more frequent in metastasized tumors, suggesting alterations of genes important for tumor progression. Sequencing of 48 genes implicated in cancer revealed that only VHL, TP53, and PTEN were mutated at a noticeable frequency (51%, 9%, and 9%, respectively). Shorter relative telomere length (RTL) has been associated with loss of specific chromosomal regions in ccRCC tumors, but we could not verify this finding. However, a significantly lower tumor/nontumor (T/N) RTL ratio was detected for tumors with losses in 4q or 9p. In conclusion, poor outcome in ccRCC was associated with gain of 7q and loss on 9p, 9q, and 14q, whereas the mutation rate overall was low in a screen of cancer-associated genes.
透明细胞肾细胞癌（ccRCC）的详细基因图谱分析揭示了通常受结构变化影响的基因组区域以及普遍存在的基因异质性。VHL和PBRM1均位于3号染色体p臂，是两个高频突变的主要基因，但除了这些畸变外，ccRCC的突变图谱在很大程度上尚不明确。基因组变化所提供的潜在预后信息似乎取决于所研究的特定队列。我们分析了一个由74例患者组成的瑞典ccRCC队列，发现在12个染色体区域（1p、3p、3q、5q、6q、7p、7q、8p、9p、9q、10q和14q）存在常见变化（在>20%的肿瘤中出现缺失或增益）。不良预后与7q增益以及9p、9q和14q缺失相关。这些畸变在转移瘤中更为常见，提示对肿瘤进展重要的基因发生了改变。对48个与癌症相关基因的测序显示，只有VHL、TP53和PTEN以显著频率发生突变（分别为51%、9%和9%）。较短的相对端粒长度（RTL）与ccRCC肿瘤中特定染色体区域的缺失有关，但我们无法证实这一发现。然而，对于在4q或9p有缺失的肿瘤，检测到肿瘤/非肿瘤（T/N）RTL比率显著较低。总之，ccRCC的不良预后与7q增益以及9p、9q和14q缺失相关，而在癌症相关基因筛查中总体突变率较低。
