Relationship Between Loss of Y Chromosome and Urologic Cancers: New Future Perspectives

Pierluigi Russo^{1

2}, Francesco Pio Bizzarri^{1

2

3

4}, Giovanni Battista Filomena^{1

2

5}, Filippo Marino^{1

2

4}, Roberto Iacovelli⁶, Chiara Ciccarese⁶, Luigi Boccuto⁷, Mauro Ragonese¹, Filippo Gavi^{1

2}, Francesco Rossi^{1

2

3}, Cosimo Savoia⁸, Paolo Pietro Suraci⁹, Roberto Falabella¹⁰, Savio Domenico Pandolfo¹¹, Luigi Napolitano¹¹, Chiara Leoni¹², Valentina Trevisan¹², Giuseppe Palermo¹, Marco Racioppi^{1

2}, Emilio Sacco^{2

3}, Stijn Muselaers¹³, Nazario Foschi¹

Affiliations

¹ Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, 00168 Rome, Italy.
² Department of Urology, Università Cattolica Del Sacro Cuore, 00168 Rome, Italy.
³ Department of Urology, Ospedale Isola Tiberina-Gemelli Isola, 00168 Rome, Italy.
⁴ Department of Urology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
⁵ Department of Urology, "F. Miulli" General Hospital, 70021 Acquaviva Delle Fonti, BA, Italy.
⁶ Department of Oncology, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, 00168 Rome, Italy.
⁷ Healthcare Genetics and Genomics, School of Nursing, Clemson University, Clemson, SC 29634, USA.
⁸ Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
⁹ Unit of Urology, Department of Medical-Surgical Sciences and Biotechnologies, Istituto Chirurgico Ortopedico Traumatologico Hospital, University of Rome Sapienza, Via F. Faggiana 1668, 04100 Latina, Italy.
¹⁰ Azienda Ospedaliera San Carlo, 85100 Potenza, Italy.
¹¹ Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", 80138 Naples, Italy.
¹² Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy.
¹³ Department of Urology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.

PMID: 39594721
PMCID: PMC11593089
DOI: 10.3390/cancers16223766

Review

Relationship Between Loss of Y Chromosome and Urologic Cancers: New Future Perspectives

Pierluigi Russo et al. Cancers (Basel). 2024.

. 2024 Nov 8;16(22):3766.

doi: 10.3390/cancers16223766.

Authors

Affiliations

¹ Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, 00168 Rome, Italy.
² Department of Urology, Università Cattolica Del Sacro Cuore, 00168 Rome, Italy.
³ Department of Urology, Ospedale Isola Tiberina-Gemelli Isola, 00168 Rome, Italy.
⁴ Department of Urology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
⁵ Department of Urology, "F. Miulli" General Hospital, 70021 Acquaviva Delle Fonti, BA, Italy.
⁶ Department of Oncology, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, 00168 Rome, Italy.
⁷ Healthcare Genetics and Genomics, School of Nursing, Clemson University, Clemson, SC 29634, USA.
⁸ Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
⁹ Unit of Urology, Department of Medical-Surgical Sciences and Biotechnologies, Istituto Chirurgico Ortopedico Traumatologico Hospital, University of Rome Sapienza, Via F. Faggiana 1668, 04100 Latina, Italy.
¹⁰ Azienda Ospedaliera San Carlo, 85100 Potenza, Italy.
¹¹ Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", 80138 Naples, Italy.
¹² Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy.
¹³ Department of Urology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.

PMID: 39594721
PMCID: PMC11593089
DOI: 10.3390/cancers16223766

Abstract

Background: The Y chromosome (ChrY) is essential for male sex determination and spermatogenesis. However, recent studies have revealed its broader role in various physiological processes and disease susceptibility, including cancer. Methods: A comprehensive literature review was conducted using databases like MEDLINE, Scopus, Web of Science, and Google Scholar. The review included clinical and preclinical studies in animals and humans focusing on the role of LoY in urological tumors. Data on the frequency of LoY, its clinical implications, and underlying mechanisms were extracted and analyzed. Results: The evidence suggests that LoY is associated with an increased risk of urologic neoplasms, potentially serving as an early marker of genomic instability. Studies reveal that LoY in urologic cancers correlates with worse survival outcomes and may contribute to tumor progression. LoY may interfere with chromatin structure and epigenetic regulation, suggesting its role as a contributor to early tumorigenesis. Conclusions: LoY appears to be a structural aberration with unique biological and clinical relevance in urologic cancers, possibly serving as a biomarker for genomic instability. Further research is necessary to identify specific Y-linked genes affected by LoY, potentially informing targeted therapies and early diagnostic strategies for these cancers.

Keywords: Y chromosome; bladder cancer; immune checkpoint inhibitors; kidney cancer; prostate cancer; testicular cancer.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

**Figure 1**
Image illustrating the main urological tumors associated with the loss of the Y chromosome and their respective genes.

See this image and copyright information in PMC

References

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Relationship Between Loss of Y Chromosome and Urologic Cancers: New Future Perspectives

Affiliations

Relationship Between Loss of Y Chromosome and Urologic Cancers: New Future Perspectives

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

LinkOut - more resources

Full Text Sources