Perrino Carmen M, Hucthagowder Vishwanathan, Evenson Michael, Kulkarni Shashikant, Humphrey Peter A
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
Department of Pathology, Yale School of Medicine, New Haven, CT, 06520-8023, USA.
Hum Pathol. 2015 Jan;46(1):9-16. doi: 10.1016/j.humpath.2014.09.001. Epub 2014 Sep 21.
Renal cell carcinoma with rhabdoid differentiation (RCC-R) in adult patients is an aggressive variant of renal cancer with no known specific genetic alterations. The aim of this study was to characterize genome-wide genetic aberrations in RCC-R via utilization of high-density single-nucleotide polymorphism (SNP) arrays. We identified 20 cases of RCC-R, which displayed both clear cell renal cell carcinoma and rhabdoid histomorphologic components. DNA was extracted from formalin-fixed, paraffin-embedded tissue (from clear cell renal cell carcinoma and RCC-R areas from each case) and subjected to high-density SNP array assay. Genetic aberrations present in 10% of cases were considered significant. In areas with clear cell histomorphology, gains were most commonly observed in chromosomes 5q (66.7%, 10/15), 7 (46.7%, 7/15), and 8q (46.7%, 7/15); and losses were most commonly identified in chromosomes 14 (60%, 9/15), 8p (46.7%, 7/15), and 22 (46.7%, 7/15). In areas with rhabdoid differentiation, gains were most commonly observed in chromosome 7 (58.8%, 10/17); and losses were most commonly identified in chromosomes 9 (70.6%, 12/17), 14 (58.8%, 10/17), 4 (52.9%, 9/17), and 17p (52.9%, 9/17). Rhabdoid cells shared many chromosomal abnormalities and exhibited a greater number of copy number variations in comparison with coexisting clear cells. Loss of 11p was specific for rhabdoid differentiation, with loss found in 29.4% of rhabdoid components compared with 0% of clear cell areas. The greater number of overall genetic alterations in the rhabdoid cells and the shared genetic background between rhabdoid and clear cell areas suggest genetic evolution of the rhabdoid cells that correlates with histomorphologic progression.
成人肾细胞癌伴横纹肌样分化（RCC-R）是一种侵袭性肾癌变体，目前尚无已知的特定基因改变。本研究的目的是通过利用高密度单核苷酸多态性（SNP）阵列来表征RCC-R中的全基因组遗传畸变。我们鉴定出20例RCC-R，其同时具有透明细胞肾细胞癌和横纹肌样组织形态学成分。从福尔马林固定、石蜡包埋组织（来自每个病例的透明细胞肾细胞癌和RCC-R区域）中提取DNA，并进行高密度SNP阵列分析。在10%的病例中出现的遗传畸变被认为具有显著性。在具有透明细胞组织形态学的区域，最常见的增益出现在5q（66.7%，10/15）、7（46.7%，7/15）和8q（46.7%，7/15）染色体上；最常见的缺失出现在14（60%，9/15）、8p（46.7%，7/15）和22（46.7%，7/15）染色体上。在具有横纹肌样分化的区域，最常见的增益出现在7号染色体上（58.8%，10/17）；最常见的缺失出现在9（70.6%，12/17）、14（58.8%，10/17）、4（52.9%，9/17）和17p（52.9%，9/17）染色体上。与共存的透明细胞相比，横纹肌样细胞共享许多染色体异常，并且表现出更多的拷贝数变异。11p缺失是横纹肌样分化所特有的，在29.4%的横纹肌样成分中发现缺失，而在透明细胞区域中为0%。横纹肌样细胞中总体遗传改变数量较多，以及横纹肌样和透明细胞区域之间共享的遗传背景表明，横纹肌样细胞的遗传进化与组织形态学进展相关。
