Three genetic developmental stages of papillary renal cell tumors: duplication of chromosome 1q marks fatal progression.
Papillary renal cell tumors (RCT) make up a cytomorphologically and biologically heterogeneous group of kidney cancers including renal cell adenomas (RCA) and renal cell carcinomas (RCC). To find genetic markers landmarking the tumor progression, we have evaluated the genetic alterations obtained by karyotyping, chromosomal and array-CGH and compared with the cytological characteristics and biological behavior of 60 papillary RCTs. Based on the genetic and clinical data, we have separated 3 groups of tumors and proposed 3 genetically defined developmental stages of papillary RCTs. Papillary RCAs are characterized by combined trisomy of chromosomes 7 and 17, whereas papillary RCCs displayed additional trisomies of 3q, 8q, 12q, 16q and 20q. In addition to the genetic changes occurring in the second group, the third group of tumors was characterized by 1q gain and 6q, 8p, 9p and 14q losses. Kaplan-Meier analysis revealed a significant association between chromosome 1q gain and deadly outcome of the disease. The cytomorphological variation and size of tumors in the second and third groups did not correlate with the clinical outcome. Therefore, we suggest that our genetic classification system landmarking papillary RCA, papillary RCC without and with progression offer a better system to characterize the tumor biology of clinical significance than a cellular/morphological classification.
Szponar
Adrianna
A
Laboratory of Molecular Oncology, Medical Faculty, Ruprecht-Karls-University, Heidelberg, Germany.
Zubakov
Dmitry
D
Pawlak
Justyna
J
Jauch
Anna
A
Kovacs
Gyula
G
D002291:Carcinoma, Papillary / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D007621:Karyotyping; D007680:Kidney Neoplasms / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D016547:Kinesins / Q000235:genetics; D008297:Male; D000072379:NIMA-Related Kinases; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D016896:Treatment Outcome; D014314:Trisomy / Q000175:diagnosis / Q000235:genetics*
D005819:Genetic Markers; D015513:Oncogene Proteins; D012333:RNA, Messenger; C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases; C502598:KIF14 protein, human; D016547:Kinesins