- AJSP（Pacheco、Sangoi、Acosta、Sirohi、Chan）：13 例终末期肾病患者的 14 个 ACD-RCC，均具筛孔状/囊性生长、嗜酸性胞质，13/14 高核仁级别，10/14 可见草酸钙结晶。
- 靶向 NGS：单基因改变少且异质，队列内无反复改变；KMT2C、SETD2、FANCA、FAT1 等在不同研究间偶有重复。
- 拷贝数分三型：获得为主型（n=7；+3、7、16、17、20）、缺失为主型（n=4；−6、9、14、19、21）与近整倍体型（n=3）。获得为主型与 TCGA-KIRP 乳头状 RCC 在 7、16、17、20 获得上重叠；同一患者的 ACD-RCC 与同时性 PRCC 臂水平谱几乎一致，仅多 3q 获得。
- 提示：形态独特的 ACD-RCC 与 PRCC 基因组相近，拷贝数模式可作为理解其异质性的框架。本站仅获摘要。
收录范围：PubMed 摘要中英对照。AJSP 全文需订阅（Ovid 页面无开放许可），本站未获全文与图表。
摘要
获得性囊性肾病相关肾细胞癌（ACD-RCC）是一种发生于终末期肾病患者、组织学特征鲜明的肾肿瘤，其分子基础仍未完全阐明。本研究对 13 例患者的 14 个 ACD-RCC 肿瘤进行了全面的靶向二代测序及拷贝数分析。所有肿瘤均具有经典组织学特征：实性筛孔状与囊性生长、胞质丰富嗜酸性，以高核仁级别为主（13/14），并不同程度可见草酸钙结晶（10/14）。序列分析中，单基因改变相对少见且异质，队列内无反复出现的改变；但文献复习显示，所检出的若干改变在不同研究间偶有重复（如 KMT2C、SETD2、FANCA 与 FAT1）。拷贝数分析识别出 3 种染色体改变模式：获得为主型（n=7）、缺失为主型（n=4）与近整倍体型（n=3）。获得为主型肿瘤反复出现 3、7、16、17 和 20 号染色体获得，缺失为主型肿瘤则反复出现 6、9、14、19 和 21 号染色体缺失；近整倍体组的染色体拷贝数改变相对较少。值得注意的是，与公开的癌症基因组图谱（TCGA）乳头状肾细胞癌（PRCC，TCGA-KIRP）数据比较，获得为主型 ACD-RCC 与其在 7、16、17 和 20 号染色体获得上相互重叠。此外，本队列中同一患者的一对 ACD-RCC 与同时性 PRCC 显示高度相似的染色体臂水平拷贝数谱，差别仅在于 ACD-RCC 多出 3q 获得。总之，尽管基因水平的发现异质，ACD-RCC 仍呈现反复出现的染色体臂水平改变模式。获得为主型肿瘤与 PRCC 存在显著的分子重叠，支持二者尽管组织形态不同、基因组却相似。这些发现还提示，拷贝数模式可作为理解 ACD-RCC 内部异质性的有用分子框架。
- AJSP (Pacheco, Sangoi, Acosta, Sirohi, Chan): 14 ACD-RCCs from 13 patients with end-stage renal disease, all with sieve-like/cystic growth and eosinophilic cytoplasm; 13/14 high nucleolar grade, calcium oxalate crystals in 10/14.
- Targeted NGS: infrequent, heterogeneous single-gene alterations with none recurrent in the cohort; KMT2C, SETD2, FANCA and FAT1 occasionally recur across studies.
- Three copy-number patterns: gain-predominant (n=7; +3, 7, 16, 17, 20), loss-predominant (n=4; −6, 9, 14, 19, 21) and near-euploid (n=3). Gain-predominant tumours overlap TCGA-KIRP papillary RCC at +7, 16, 17, 20; a paired ACD-RCC and synchronous PRCC from one patient had near-identical arm-level profiles apart from 3q gain.
- Implication: despite distinct morphology, ACD-RCC is genomically close to PRCC, and copy-number patterns offer a framework for its heterogeneity. Abstract only.
Scope: PubMed abstract. The AJSP full text is subscription-only (no open licence on the Ovid page); full text and figures were not obtained.
Abstract
Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is a histologically distinctive renal neoplasm arising in patients with end-stage renal disease, in which the molecular underpinnings remain incompletely characterized. In this study, 14 ACD-RCC tumors from 13 patients underwent comprehensive targeted next-generation sequencing with copy-number analysis. All tumors had classic histologic features characterized by solid sieve-like and cystic growth with abundant eosinophilic cytoplasm, predominantly high nucleolar grade (13/14), and variably present calcium oxalate crystals (10/14). By sequence analysis, single-gene alterations were relatively infrequent and heterogenous, with no recurrent alterations within the cohort; though several alterations identified were occasionally recurrent across studies on literature review (eg, KMT2C, SETD2, FANCA, and FAT1). Copy-number analysis identified 3 patterns of chromosomal alterations: gain-predominant (n=7), loss-predominant (n=4), and near-euploid (n=3) subgroups. Gain-predominant tumors harbored recurrent gains of chromosomes 3, 7, 16, 17, and 20, whereas loss-predominant tumors showed recurrent losses of chromosomes 6, 9, 14, 19, and 21. The near-euploid group had relatively fewer chromosomal copy-number alterations. Notably, comparison with publicly available The Cancer Genome Atlas papillary renal cell carcinoma (PRCC, TCGA-KIRP) data demonstrated overlapping gains of chromosomes 7, 16, 17, and 20 with the gain-predominant ACD-RCC. In addition, a paired ACD-RCC and synchronous PRCC from the same patient in our cohort displayed highly similar arm-level copy-number profiles, differing only by an additional gain of chromosome 3q in the ACD-RCC. In summary, ACD-RCC demonstrates recurrent arm-level chromosomal alteration patterns despite heterogenous gene-level findings. The gain-predominant tumors show substantial molecular overlap with PRCC, supporting genomic similarity between these entities despite distinct histomorphology. Together, these findings also suggest that copy-number patterns may represent a useful molecular framework for understanding heterogeneity within ACD-RCC.