title: Dismantling papillary renal cell carcinoma classification: The heterogeneity of genetic profiles suggests several independent diseases.
abstract: Papillary renal cell carcinoma (pRCC) is the second most frequent renal cell carcinoma (RCC) after clear cell RCC. In contrast to clear cell RCC, there is no consensual protocol using targeted therapy for metastatic pRCC. Moreover, diagnosis of some pRCC, especially pRCC of type 2 (pRCC2) may be challenging. Our aim was to identify molecular biomarkers that could be helpful for the diagnosis and treatment of pRCC. We studied the clinical, histological, immunohistological, and comprehensive genetic features of a series of 31 pRCC including 15 pRCC1 and 16 pRCC2. We aimed to determine whether pRCC represents a unique entity or several diseases. In addition, we compared the genetic features of pRCC2 to those of eight RCC showing various degrees of tubulo-papillary architecture, including three TFE-translocation RCC and five unclassified RCC. We demonstrate that pRCC is a heterogeneous group of tumors with distinct evolution. While most pRCC2 had genetic profiles similar to pRCC1, some shared genomic features, such as loss of 3p and loss of chromosome 14, with clear cell RCC, TFE-translocation RCC, and unclassified RCC. We identified variants of the MET gene in three pRCC1. A mutation in the BRAF gene was also identified in one pRCC1. In addition, using next-generation sequencing (NGS), we identified several variant genes. Genomic profiling completed by NGS allowed us to classify pRCC2 in several groups and to identify novel mutations. Our findings provide novel information on the pathogenesis of pRCC that allow insights for personalized treatment.
authors.affiliation: Institute for Research on Cancer and Aging of Nice (IRCAN), CNRS UMR 7284/INSERM U1081, University of Nice-Sophia Antipolis, Nice, France; Department of Urology, Nice University Hospital, Nice, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Marsaud
authors.forename: Bérengère
authors.initials: B
authors.lastname: Dadone
authors.forename: Damien
authors.initials: D
authors.lastname: Ambrosetti
authors.forename: Christian
authors.initials: C
authors.lastname: Baudoin
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Chamorey
authors.forename: Etienne
authors.initials: E
authors.lastname: Rouleau
authors.forename: Cédrick
authors.initials: C
authors.lastname: Lefol
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Roussel
authors.forename: Thibault
authors.initials: T
authors.lastname: Fabas
authors.forename: Gaël
authors.initials: G
authors.lastname: Cristofari
authors.forename: Xavier
authors.initials: X
authors.lastname: Carpentier
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Michiels
authors.forename: Jean
authors.initials: J
authors.lastname: Amiel
authors.forename: Florence
authors.initials: F
authors.lastname: Pedeutour
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000145:classification / Q000235:genetics* / Q000473:pathology; D002886:Chromosomes, Human, Pair 17; D002897:Chromosomes, Human, Pair 7; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor