Cytogenetics of papillary renal cell tumors

Abstract

Chromosome aberrations were determined in short-term cultures of 18 papillary renal cell tumors, as well as in the cell line ACHN, and the results were evaluated together with 20 previously published cases. We found that chromosomes 7, 17, and 16 and the Y chromosome were specifically involved in the karyotype changes, marks benign papillary renal cell adenomas (ten cases). Malignant papillary renal cell carcinomas (29 cases) were characterized by additional trisomies: trisomy 16 occurred in 20 tumors, and trisomy 12 and 20 in 8 tumors each. Loss of the Y chromosome was observed in 7 of 9 benign and in 23 of 25 malignant tumors that developed in males. None of the papillary renal cell adenomas or carcinomas showed a loss of 3p or gain of a 5q segment, both of which are characteristic of common non-papillary renal cell carcinomas.

Renal mucinous tubular and spindle carcinoma lacks the gains of chromosomes 7 and 17 and losses of chromosome Y that are prevalent in papillary renal cell carcinoma

“…These chromosomal abnormalities occur early in the evolution of papillary renal cell neoplasia and are often associated with further gains of chromosomes 12, 16 and 20. 17,[23][24][25][26][27][28][34][35][36] The typical gains of chromosome 7 and 17 and loss of Y in papillary renal cell carcinomas have been observed in several FISH-based studies, and FISH analyses with centromeric probes for chromosomes 7, 17 and Y have been previously proposed to have a potential role in the differential diagnosis of papillary renal cell tumors with metanephric adenomas. 25,27,32,35,37 Furthermore, recent studies performed with multicolor FISH confirmed the typical chromosomal abnormalities described in papillary renal cell carcinomas and interphase FISH may be considered as a sensitive and specific technique for a rapid and accurate identification of distinctive genetic abnormalities, that are potentially useful in the distinction of the different histotypes of renal cell carcinomas.…”

“…Both tumors frequently express cytokeratin 7, epithelial membrane antigen, high molecular weight cytokeratin and a-methylacyl-CoA racemase. 22 While genetic abnormalities in papillary renal cell carcinomas have been extensively studied, [23][24][25][26][27][28][29] so far, genetic studies on mucinous tubular and spindle cell carcinomas are few and mainly based on comparative genomic hybridization. 9,13,30,31 Fluorescence in situ hybridization (FISH) has proved useful in distinguishing papillary renal cell carcinoma from metanephric adenoma, with which it may also be confused.…”

Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene

“…In papillary RCC, frequently detected genetic alterations include trisomy of chromosomes 3q, 7, 8, 12, 16, 17 and 20, and loss of the Y chromosome (Kovacs et al, 1991;Jiang et al, 1998). Although the MET proto-oncogene (7q31) is implicated in the pathogenesis of papillary RCC, only a small percentage of the cases of the sporadic papillary RCC have MET mutations (Schmidt et al, 1997).…”

Fusion of splicing factor genes PSF and NonO (p54nrb) to the TFE3 gene in papillary renal cell carcinoma

“…A high frequency of loss of chromosome Y and trisomy of chromosome 7 has, however, been reported in papillary RCC (Kovacs et al, 1987(Kovacs et al, , 1991Kovacs, 1993;van den Berg et al, 1993;Elfving et al, 1995) and a speci®c translocation between chromosomes X and 1, t(X;1)(p11.2;q21.2), has been identi®ed in cytogenetic studies (de Jong et al, 1986;Meloni et al, 1993;Mitelman, 1994;Shipley et al, 1995;Tonk et al, 1995). It has recently been shown (Sidhar et al, 1996;Weterman et al, 1996a, b) that this translocation results in the fusion of a novel chromosome 1 gene, called PRCC, to the chromosome X gene TFE3, which encodes a member of the basic-helix ± loop ± helix family of transcription factors originally identi®ed by its ability to bind to mE3 elements in the immunoglobin heavy chain intronic enhancer (Beckmann et al, 1990).…”