Why loss of Y? A pan-cancer genome analysis of tumors with loss of Y chromosome

Müller, Philipp; Camacho, Oscar Velazquez; Yazbeck, Ali M.; Wölwer, Christina B.; Zhai, Weiwei; Schumacher, Johannes; Heider, Dominik; Büttner, Reinhard; Quaas, Alexander; Hillmer, Axel M.

doi:10.1016/j.csbj.2023.02.024

Cited by 9 publications

(11 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Loss of chromosome Y has also been shown as a very frequent mutation in tumor cells from numerous cancers and LOY correlates with an overall worse prognosis 47 , 48 . This agrees with the concept that LOY provides proliferative advantage to cells affected by this aneuploidy 49 .…”

Section: Discussionmentioning

confidence: 99%

Loss of Y in regulatory T lymphocytes in the tumor micro-environment of primary colorectal cancers and liver metastases

Wójcik,

Juhas,

Mohammadi

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Male sex is a risk factor for colorectal cancer (CRC) with higher illness burden and earlier onset. Thus, we hypothesized that loss of chromosome Y (LOY) in the tumor micro-environment (TME) might be involved in oncogenesis. Previous studies show that LOY in circulating leukocytes of aging men was associated with shorter survival and non-hematological cancer, as well as higher LOY in CD4 + T-lymphocytes in men with prostate cancer vs. controls. However, nothing is known about LOY in leukocytes infiltrating TME and we address this aspect here. We studied frequency and functional effects of LOY in blood, TME and non-tumorous tissue. Regulatory T-lymphocytes (Tregs) in TME had the highest frequency of LOY (22%) in comparison to CD4 + T-lymphocytes and cytotoxic CD8 + T-lymphocytes. LOY score using scRNA-seq was also linked to higher expression of PDCD1, TIGIT and IKZF2 in Tregs. PDCD1 and TIGIT encode immune checkpoint receptors involved in the regulation of Tregs function. Our study sets the direction for further functional research regarding a probable role of LOY in intensifying features related to the suppressive phenotype of Tregs in TME and consequently a possible influence on immunotherapy response in CRC patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Loss of Y in regulatory T lymphocytes in the tumor micro-environment of primary colorectal cancers and liver metastases

Wójcik,

Juhas,

Mohammadi

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In fact, although LOY has been reported as a para-physiologic aging consequence in elderly men [ 54 ], it has also been observed in cancer tissues, where it is associated with an overall worse prognosis. It is the case, among the others, of kidney renal papillary cell carcinoma, esophageal adenocarcinoma and male breast cancer, enumerated amongst the most aggressive malignancies, with high genomic instability, aneuploidy, as well as an augmented mutation burden [ 55 , 56 ]. LOY has been found to affect also 33–36% of cases of pancreatic cancer and 23–34% of bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

CRISPR/Cas9 mediated Y-chromosome elimination affects human cells transcriptome

Celli,

Gasparini,

Biino

et al. 2024

Cell Biosci

View full text Add to dashboard Cite

Background Sexual dimorphism represents a key concept in the comprehension of molecular processes guiding several sex-specific physiological and pathological mechanisms. It has been reported that genes involved in many disorders show a sex-dependent expression pattern. Moreover, the loss of Y chromosome (LOY), found to be a physiological age-driven phenomenon, has been linked to many neurodegenerative and autoimmune disorders, and to an increased cancer risk. These findings drove us towards the consideration that LOY may cause the de-regulation of disease specific networks, involving genes located in both autosomal and sex chromosomes. Results Exploiting the CRISPR/Cas9 and RNA-sequencing technologies, we generated a Y-deficient human cell line that has been investigated for its gene expression profile. Our results showed that LOY can influence the transcriptome displaying relevant enriched biological processes, such as cell migration regulation, angiogenesis and immune response. Interestingly, the ovarian follicle development pathway was found enriched, supporting the female-mimicking profile of male Y-depleted cells. Conclusion This study, besides proposing a novel approach to investigate sex-biased physiological and pathological conditions, highlights new roles for the Y chromosome in the sexual dimorphism characterizing human health and diseases. Moreover, this analysis paves the way for the research of new therapeutic approaches for sex dimorphic and LOY-related diseases.

show abstract

“…[44][45][46][47][48][49] Recent advancements in the field have been greatly facilitated by the availability of extensive datasets, including those from large databases like The Cancer Genome Atlas (TCGA), which have comprehensively mapped genetic mutations. 27,50 The presence of mLOY in caner tissues is determined by assessing the reduced expression of Y chromosome genes. If the expression level of Y falls below that observed in females, it is designated as mLOY.…”

Section: Y Chromosome Loss In C An Cer Cell Smentioning

confidence: 99%

“…The loss of Y chromosome has been observed in various cancer types 44–49 . Recent advancements in the field have been greatly facilitated by the availability of extensive datasets, including those from large databases like The Cancer Genome Atlas (TCGA), which have comprehensively mapped genetic mutations 27,50 . The presence of mLOY in caner tissues is determined by assessing the reduced expression of Y chromosome genes.…”

Section: Y Chromosome Loss In Cancer Cellsmentioning

confidence: 99%

Why Y matters? The implication of loss of Y chromosome in blood and cancer

Wang,

Sano

2024

Cancer Science

View full text Add to dashboard Cite

Hematopoietic mosaic loss of Y chromosome (mLOY) has emerged as a potential male‐specific accelerator of biological aging, increasing the risk of various age‐related diseases, including cancer. Importantly, mLOY is not confined to hematopoietic cells; its presence has also been observed in nonhematological cancer cells, with the impact of this presence previously unknown. Recent studies have revealed that, whether occurring in leukocytes or cancer cells, mLOY plays a role in promoting the development of an immunosuppressive tumor microenvironment. This occurs through the modulation of tumor‐infiltrating immune cells, ultimately enabling cancer cells to evade the vigilant immune system. In this review, we illuminate recent progress concerning the effects of hematopoietic mLOY and cancer mLOY on cancer progression. Examining cancer progression from the perspective of LOY adds a new layer to our understanding of cancer immunity, promising insights that hold the potential to identify innovative and potent immunotherapy targets for cancer.

show abstract

Why loss of Y? A pan-cancer genome analysis of tumors with loss of Y chromosome

Cited by 9 publications

References 54 publications

Loss of Y in regulatory T lymphocytes in the tumor micro-environment of primary colorectal cancers and liver metastases

Loss of Y in regulatory T lymphocytes in the tumor micro-environment of primary colorectal cancers and liver metastases

CRISPR/Cas9 mediated Y-chromosome elimination affects human cells transcriptome

Why Y matters? The implication of loss of Y chromosome in blood and cancer

Contact Info

Product

Resources

About