Genetics and genomics of prostate cancer. (original) (raw)

Major Candidate Genes Associated with Risk of Hereditary and Sporadic Prostate Cancer

Prostate cancer risk factors gain more awareness in the world nowadays, due to the increasing incidents, which vary among different ethnic groups. Researches about genetic risk factors might help for more understanding of the initiation and development of prostate cancer and estimating risk values among individuals, and develop multi-perspective therapy approaches. Many efforts were achieved to study and evaluate high-risk variants associated with prostate tumors; through different populations. This evaluation depended on the high frequencies of these variants and the role of such variants in cell cycle and DNA repairing system. In this review, we highlighted the major candidate genes and molecular events of prostate cancer: BRCA, CHEK2, HOXB13, ELAC2, SPOP, PTEN, TMPRSS2-ERG Fusion and other less effective variants, in an attempt to explore the molecular seriousness and relative risk of suspected variants associated with hereditary and sporadic prostate cancer. The definition of particular groups of genes that lead prostate cancer prognosis is a difficult task, since the genetic and proteomic studies detected numerous susceptibility alleles complicated with risk of prostate tumors. The estimation of high-risk variants may be a key issue regarding prostate cancer diagnosis and therapy.

Genomics of Prostate Cancer: Clinical Utility and Challenges

Acta Clinica Croatica, 2022

The studying of prostate cancer genomics is important for understanding prostate cancer biology, it can provide clinically relevant stratification into subtypes, the development of new prognostic and predictive markers in the context of precision medicine, and the development of new targeted therapies. Recent studies have provided detailed insight into genomics, epigenomics and proteomics of prostate cancer, both primary and metastatic castration-resistant (mCRPC). Many mutations have been discovered, both those that occur early in the carcinogenesis and progression as well as those responsible for the resistance to therapy occurring later under the influence of treatment. A large number of characteristic mutated signaling pathways has been identified, e.g. the mutations in DNA repair pathway were found in 23% of mCRPC, which suggests potential response to PARP inhibitors. Multifocality and intralesional genomic heterogeneity of prostate cancer make the clinical application of genomics complicated. Although a great progress was made in understanding prostate cancer genomic, and clinical studies related to its routine application are ongoing, prostate cancer genomics still needs to find its standard wide routine application in patients with prostate cancer.

Genetics of Prostate Carcinoma

Acta Medica Academica, 2021

The aim of this review is to provide a brief overview of some current approaches regarding diagnostics, pathologic features, treatment, and genetics of prostate carcinoma (PCa). Prostate carcinoma is the most common visceral tumor and the second most common cancer-related cause of death in males. Clinical outcomes for patients with localized prostate cancer are excellent, but despite advances in prostate cancer treatments, castrate-resistant prostate cancer and metastatic prostate cancer patients have a poor prognosis. Advanced large-scale genomic studies revealed a large number of genetic alterations in prostate cancer. The meaning of these alterations needs to be validated in the specific prostate cancer molecular subtype context. Along these lines, there is a critical need for establishing genetically engineered mouse models, which would include speckle type BTB/POZ protein and isocitrate Dehydrogenase (NADP (+)) 1 mutant, as well as androgen receptor neuroendocrine subtypes of p...

Molecular biology of prostate cancer

Molecular Human Reproduction, 2003

In spite of progress in diagnosis and treatment, prostate cancer has become one of the most frequent lethal cancers in males in many Western industrialized countries. Research on the molecular biology of prostate cancer is expected to reveal those aspects of Western lifestyle contributing to its high incidence with the aims of improving prevention, distinguishing slow-growing from aggressive clinically relevant cancers, and providing targets for treatment, particularly of locally advanced and of metastatic disease. Traditionally, prostate cancer research focused on androgens. More recently, tumour suppressors and proto-oncogenes important in other human cancers have been intensely investigated. Current approaches include the search for genes mutated in familial cases, identi®cation of recurrent chromosomal alterations and their associated potential tumour suppressor genes, determination of gene expression pro®les characterizing tumour stages and subclasses, and elucidation of the importance of epigenetic alterations. Results from such studies have begun to be translated into the clinic. Further successful transfer of results from molecular biology to the clinic will, however, require integration of the amassed molecular data into a biological framework model of prostate carcinoma.

Prostate Cancer Review: Genetics, Diagnosis, Treatment Options, and Alternative Approaches

Molecules

Prostate cancer is one of the malignancies that affects men and significantly contributes to increased mortality rates in men globally. Patients affected with prostate cancer present with either a localized or advanced disease. In this review, we aim to provide a holistic overview of prostate cancer, including the diagnosis of the disease, mutations leading to the onset and progression of the disease, and treatment options. Prostate cancer diagnoses include a digital rectal examination, prostate-specific antigen analysis, and prostate biopsies. Mutations in certain genes are linked to the onset, progression, and metastasis of the cancer. Treatment for localized prostate cancer encompasses active surveillance, ablative radiotherapy, and radical prostatectomy. Men who relapse or present metastatic prostate cancer receive androgen deprivation therapy (ADT), salvage radiotherapy, and chemotherapy. Currently, available treatment options are more effective when used as combination therapy...

The genetics of neuroendocrine prostate cancers: a review of current and emerging candidates

The Application of Clinical Genetics, 2012

Prostate cancer (PC) displays a strong familial link and genetic factors; genes regulating inflammation may have a pivotal role in the disease. Epigenetic changes control chromosomal integrity, gene functions, and, ultimately, carcinogenesis. The most widely studied epigenetic event in PC is aberrant DNA methylation (hypo-and hypermethylation); besides this, chromatin remodeling and micro RNA (miRNA) are other studied alterations in PC. These all lead to genomic instability and inappropriate gene expression. Causative dysfunction of histone modifying enzymes results in generic and locus-specific changes in chromatin remodeling. miRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen-receptor signaling and apoptosis. These epigenetic alterations have the potential to act as biomarkers for PC for screening and diagnosis as well as prognosis and follow-up. The variable biological potential for a newly diagnosed PC is one of the biggest challenges. The other major clinical problem is in the management of castration-resistant PC. Neuroendocrine (NE) differentiation is one of the putative explanations for the development of castration-resistant disease. Most advanced and poorly differentiated cancer does not produce prostate-specific antigen (PSA) in response to disease progression. Circulating and tissue biomarkers like chromogranin A (CgA) thus become important tools. There is the potential to use various genetic and epigenetic alterations and NE differentiation as therapeutic targets in the management of PC. However, we are still some distance from developing clinically effective tools. Valuable insights into the nature of NE differentiation in PC have been gained in the last decades, but additional understanding of its pathogenetic mechanisms is needed. This will help in devising novel therapeutic strategies to develop targeted therapies. CgA has the potential to become an important marker of advanced castration-resistant PC in cases where prostate-specific antigen can no longer be relied upon. Aberrant androgen-receptor signaling at various levels provides evidence of the importance of this pathway for the development of castration-resistant PC. Many epigenetic influences-in particular, the role of changing miRNA expression-provide valuable insights. Currently, massive sequencing efforts are underway to define important somatic genetic alterations (amplifications, deletions, point mutations, translocations) in PC, and these alterations hold great promise as prognostic markers and for predicting response to therapy.

Molecular biology of prostate-cancer pathogenesis

Current Opinion in Urology, 2006

The genetic and molecular basis of prostate-cancer pathogenesis is reviewed. Recent findings Several genetic loci have been found that are associated with hereditary predisposition to prostate cancer, but they account for a small fraction of all cases. A number of suppressor genes have been identified that are activated by either complete or partial genetic loss in sporadic prostate cancer. Chromosomal translocation results in transcriptional activation of truncated ETS transcription factors ERG and ETV1, the first candidates for dominant oncogenes for prostate cancer. Lastly, the androgen receptor is active throughout the course of prostate cancer and, in androgen-independent prostate cancer, takes on the role of a dominant oncogene as the target of gene amplification, overexpression, and the activation of mutations. Summary Genetic lesions responsible for familial and sporadic prostate cancer are being revealed and they suggest that prostate cancer often initiates owing to an increased susceptibility to oxidative damage; it then progresses by affecting transcription factors, the PI3 kinase pathway, and other growth stimulatory pathways. The final common pathway after androgen ablation appears to be activation of androgen receptor.

Genetics and Clinical Genomics Characterization of new genes involved in prostate cancer metastasis

Introduction: Our work addresses a literature review conducted between January 2019 and September 2023, the importance of BRCA1, BRCA2, AR and PTEN genes in the pathogenesis, prognosis and treatment of prostate cancer, especially in its metastatic castration-resistant form (mCRPC), is highlighted. BRCA1 and BRCA2 genes are identified as key markers for predicting cancer aggressiveness, suggesting the need for targeted therapies and strict surveillance. The adaptability of cancer cells and variability in androgen receptor (AR) expression limit the effectiveness of therapies focused solely on AR, pointing to the importance of identifying alternative pathways and biomarkers for more effective treatment. PTEN function is directly related to disease progression, and its alteration suggests potential therapeutic approaches. However, the heterogeneity of cancer cells and complexity of molecular pathways present significant challenges to the development of universal therapies. Conclusion: The findings promote future research to confirm the applicability of these genes as biomarkers and to develop personalized treatment strategies in prostate cancer.