J 2017

Loss of chromosome Y leads to down regulation of KDM5D and KDM6C epigenetic modifiers in clear cell renal cell carcinoma

ARSENEAULT, M., J. MONLONG, N.S. VASUDEV, R.S. LASKAR, M. SAFISAMGHABADI et. al.

Základní údaje

Originální název

Loss of chromosome Y leads to down regulation of KDM5D and KDM6C epigenetic modifiers in clear cell renal cell carcinoma

Autoři

ARSENEAULT, M. (124 Kanada), J. MONLONG (124 Kanada), N.S. VASUDEV (124 Kanada), R.S. LASKAR (124 Kanada), M. SAFISAMGHABADI (124 Kanada), P. HARNDEN (826 Velká Británie a Severní Irsko), L. EGEVAD (203 Česká republika), N. NOURBEHESHT (124 Kanada), P. PANICHNANTAKUL (826 Velká Británie a Severní Irsko), I. HOLCATOVA (826 Velká Británie a Severní Irsko), A. BRISUDA (124 Kanada), V. JANOUT (124 Kanada), H. KOLLAROVA (124 Kanada), Lenka FORETOVÁ (203 Česká republika, garant, domácí), M. NAVRATILOVA (203 Česká republika), D. MATES (124 Kanada), V. JINGA (124 Kanada), D. ZARIDZE (56 Belgie), A. MUKERIA (56 Belgie), P. JANDAGHI (250 Francie), P. BRENNAN (203 Česká republika), A. BRAZMA (643 Rusko), J. TOST (642 Rumunsko), G. SCELO (124 Kanada), R.E. BANKS (124 Kanada), M. LATHROP (124 Kanada), G. BOURQUE (124 Kanada) a Y. RIAZALHOSSEINI (124 Kanada)

Vydání

Scientific Reports, LONDON, NATURE PUBLISHING GROUP, 2017, 2045-2322

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 4.122

Kód RIV

RIV/00216224:14110/17:00098730

Organizační jednotka

Lékařská fakulta

UT WoS

000397186600001

Klíčová slova anglicky

KDM5D; KDM6C

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 21. 3. 2018 16:19, Soňa Böhmová

Anotace

V originále

Recent genomic studies of sporadic clear cell renal cell carcinoma (ccRCC) have uncovered novel driver genes and pathways. Given the unequal incidence rates among men and women (male:female incidence ratio approaches 2:1), we compared the genome-wide distribution of the chromosomal abnormalities in both sexes. We observed a higher frequency for the somatic recurrent chromosomal copy number variations (CNVs) of autosomes in male subjects, whereas somatic loss of chromosome X was detected exclusively in female patients (17.1%). Furthermore, somatic loss of chromosome Y (LOY) was detected in about 40% of male subjects, while mosaic LOY was detected in DNA isolated from peripheral blood in 9.6% of them, and was the only recurrent CNV in constitutional DNA samples. LOY in constitutional DNA, but not in tumor DNA was associated with older age. Amongst Y-linked genes that were downregulated due to LOY, KDM5D and KDM6C epigenetic modifiers have functionally-similar X-linked homologs whose deficiency is involved in ccRCC progression. Our findings establish somatic LOY as a highly recurrent genetic defect in ccRCC that leads to downregulation of hitherto unsuspected epigenetic factors, and suggest that different mechanisms may underlie the somatic and mosaic LOY observed in tumors and peripheral blood, respectively.