Acquired Cystic Disease-Associated Renal Cell Carcinoma

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.