Fumarate hydratase deficient renal cell carcinoma: Chromosomal numerical aberration analysis of 12 cases

• DOI: 10.1016/j.anndiagpath.2019.02.008
• Publication Date: 2019-02-11T00:00:08Z
• Authors: Kristyna Pivovarc...; Petr Martinek; Petr Grossmann; Kiril Trpkov; Reza Alaghehbandan; Cristina Magi-Gal...; Maria Pane Foix; Enric Condom Mundo; Daniel Berney; Anthony Gill; Boris Rychly; Kvetoslava Michalova; Joanna Rogala; Tomas Pitra; Tamas Micsik; Jiri Polivka; Milan Hora; Ozlem Tanas Isikci; Sarka Skalova; Jana Mareckova; Michal Michal; Ondrej Hes
• Keywords: Comparative genomic hybridization

Hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinoma (HLRCC)/fumarate hydratase deficient renal cell carcinoma (FHRCC) is defined by molecular genetic changes (mutation/LOH in fumarate hydratase (FH) gene). We investigated chromosomal numerical aberration pattern (CNV) in FHRCC/HLRCC using array comparative genomic hybridization analysis and low pass whole genome sequencing. Genetic analysis was successfully completed in 12 tumors. Most common chromosomal aberrations detected were a complete or partial loss of chromosome 4 (5/12 cases), chromosome 15 (4/12 cases), and chromosomes 9, 13, and 14 (each in 3/12 cases), as well as a complete or partial gain of chromosome 17 (in 4/12 cases). No chromosomal losses or gains were detected in 4 cases. Copy number variation pattern in FHRCC/HLRCC appears to be highly variable and does not provide a useful diagnostic tool in identifying these cases. Immunohistochemical staining and especially molecular genetic evaluation of FH gene mutations/LOH remain the gold standard in identifying FHRCC/HLRCC.