Y chromosome losses are exceedingly rare in prostate cancer and unrelated to patient age

Stahl, Phillip; Kilgué, Adisa; Tennstedt, Pierre; Minner, Sarah; Krohn, Antje; Simon, Ronald; Krause, G.; Izbicki, Jakob R.; Graefen, Markus; Sauter, Guido; Schlomm, Thorsten; Wilczak, Waldemar

doi:10.1002/pros.21492

Cited by 11 publications

(11 citation statements)

References 28 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The DNA methylation on the Y chromosome is relatively stable. This indicates that the Y chromosome is not as fragile as previously suggested [ 51 , 53 – 56 ]. The function and phenotypes of human males have been protected by a stable DNA methylation pattern for tens of thousands of years.…”

Section: Discussionsupporting

confidence: 74%

Epigenetic Pattern on the Human Y Chromosome Is Evolutionarily Conserved

et al. 2016

View full text Add to dashboard Cite

DNA methylation plays an important role for mammalian development. However, it is unclear whether the DNA methylation pattern is evolutionarily conserved. The Y chromosome serves as a powerful tool for the study of human evolution because it is transferred between males. In this study, based on deep-rooted pedigrees and the latest Y chromosome phylogenetic tree, we performed epigenetic pattern analysis of the Y chromosome from 72 donors. By comparing their respective DNA methylation level, we found that the DNA methylation pattern on the Y chromosome was stable among family members and haplogroups. Interestingly, two haplogroup-specific methylation sites were found, which were both genotype-dependent. Moreover, the African and Asian samples also had similar DNA methylation pattern with a remote divergence time. Our findings indicated that the DNA methylation pattern on the Y chromosome was conservative during human male history.

show abstract

Section: Discussionsupporting

confidence: 74%

Epigenetic Pattern on the Human Y Chromosome Is Evolutionarily Conserved

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Loss of the entire Y chromosome (LOY) has been reported with various frequencies in prostate [133][134][135] , pancreatic 136 , colorectal 137 and bladder 138 , which has also a strong male prevalence. Short arm deletions have also been found in numerous cancer types 139 (http://cgap.nci.nih.gov/Chromosomes/Mitelman).…”

Section: B) Y Chromosomementioning

confidence: 99%

Sexual dimorphism in cancer

et al. 2016

View full text Add to dashboard Cite

The incidence of many cancer types is significantly higher in the male than female populations, with associated differences in survival. Occupational and/or behavioral factors are well known underlying determinants. However, cellular/molecular differences between the two sexes are also likely to be important. We are focusing here on the complex interplay that sexual hormones and sex chromosomes can have in intrinsic control of cancer initiating cell populations, tumor microenvironment and systemic determinants of cancer development like the immune system and metabolism. A better appreciation of these differences between the two sexes could be of substantial value for cancer prevention as well as treatment.3 Introduction (Epidemiology)

show abstract

“…The entire or partial regions of the male-specific Y chromosome are deleted in up to 52% of prostate tumors, although the entire loss of the Y chromosome may be rare in these male-specific tumors (14). Of interest, alterations of the Y chromosome also occur in other types of cancer, including testicular tumors, male-predominant esophageal tumors (about 33%), male bladder tumors (10-40%), and male pancreatic tumors (15-19).…”

Section: Introductionmentioning

confidence: 99%

JARID1D Is a Suppressor and Prognostic Marker of Prostate Cancer Invasion and Metastasis

et al. 2016

View full text Add to dashboard Cite

Entire or partial deletions of the male-specific Y chromosome are associated with tumorigenesis, but whether any male-specific genes located on this chromosome play a tumor-suppressive role is unknown. Here, we report that the histone H3 lysine 4 (H3K4) demethylase JARID1D (also called KDM5D and SMCY), a male-specific protein, represses gene expression programs associated with cell invasiveness and suppresses the invasion of prostate cancer cells in vitro and in vivo. We found that JARID1D specifically repressed the invasion-associated genes MMP1, MMP2, MMP3, MMP7, and Slug by demethylating trimethyl H3K4, a gene-activating mark, at their promoters. Our additional results demonstrated that JARID1D levels were highly downregulated in metastatic prostate tumors compared to normal prostate tissues and primary prostate tumors. Furthermore, the JARID1D gene was frequently deleted in metastatic prostate tumors, and low JARID1D levels were associated with poor prognosis in prostate cancer patients. Taken together, these findings provide the first evidence that an epigenetic modifier expressed on the Y chromosome functions as an anti-invasion factor to suppress the progression of prostate cancer. Our results also highlight a preclinical rationale for using JARID1D as a prognostic marker in advanced prostate cancer.

show abstract

Y chromosome losses are exceedingly rare in prostate cancer and unrelated to patient age

Cited by 11 publications

References 28 publications

Epigenetic Pattern on the Human Y Chromosome Is Evolutionarily Conserved

Epigenetic Pattern on the Human Y Chromosome Is Evolutionarily Conserved

Sexual dimorphism in cancer

JARID1D Is a Suppressor and Prognostic Marker of Prostate Cancer Invasion and Metastasis

Contact Info

Product

Resources

About