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Dismantling papillary renal cell carcinoma classification: The heterogeneity of genetic profiles suggests several independent diseases
Author(s) -
Marsaud Alexandre,
Dadone Bérengère,
Ambrosetti Damien,
Baudoin Christian,
Chamorey Emmanuel,
Rouleau Etienne,
Lefol Cédrick,
Roussel JeanFrançois,
Fabas Thibault,
Cristofari Gaël,
Carpentier Xavier,
Michiels JeanFrançois,
Amiel Jean,
Pedeutour Florence
Publication year - 2015
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22248
Subject(s) - papillary renal cell carcinomas , renal cell carcinoma , comparative genomic hybridization , chromosomal translocation , genetic heterogeneity , clear cell , medicine , cancer research , biology , pathology , gene , bioinformatics , oncology , chromosome , genetics , phenotype
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. © 2015 Wiley Periodicals, Inc.