Array comparative genomic hybridization identifies a distinct DNA copy number profile in renal cell cancer associated with hereditary leiomyomatosis and renal cell cancer.
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumor predisposition syndrome with cutaneous and uterine leiomyomatosis as well as renal cell cancer (RCC) as its clinical manifestations. HLRCC is caused by heterozygous germline mutations in the fumarate hydratase (fumarase) gene. In this study, we used array comparative genomic hybridization to identify the specific copy number changes characterizing the HLRCC-associated RCCs. The study material comprised formalin-fixed paraffin-embedded renal tumors obtained from Finnish patients with HLRCC. All 11 investigated tumors displayed the papillary type 2 histopathology typical for HLRCC renal tumors. The most frequent copy number changes detected in at least 3/11 (27%) of the tumors were gains in chromosomes 2, 7, and 17, and losses in 13q12.3-q21.1, 14, 18, and X. These findings provide genetic evidence for a distinct copy number profile in HLRCC renal tumors compared with sporadic RCC tumors of the same histopathological subtype, and delineate chromosomal regions that associate with this very aggressive form of RCC.
Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Taru A
TA
Koski
Heli J
HJ
Lehtonen
Kowan J
KJ
Jee
Shinsuke
S
Ninomiya
Simon A
SA
Joosse
Pia
P
Vahteristo
Maija
M
Kiuru
Auli
A
Karhu
Heli
H
Sammalkorpi
Sakari
S
Vanharanta
Rainer
R
Lehtonen
Henrik
H
Edgren
Petra M
PM
Nederlof
Marja
M
Hietala
Kristiina
K
Aittomäki
Riitta
R
Herva
Sakari
S
Knuutila
Lauri A
LA
Aaltonen
Virpi
V
Launonen
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D018231:Leiomyomatosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional