Department of Physiology and Biophysics, Stony Brook University School of Medicine, Stony Brook, NY, USA.
Medical Student Research Institute, St. George's University School of Medicine, St. George's, Grenada.
Prostate Cancer Prostatic Dis. 2018 Apr;21(1):22-36. doi: 10.1038/s41391-017-0023-8. Epub 2017 Dec 27.
With continuous progress over the past few decades in understanding diagnosis, treatment, and genetics, much has been learned about the prostate cancer-diagnosed genome.
A comprehensive MEDLINE® and Google scholar literature search was conducted using keyword variations relating to the genetics of prostate cancer such as chromosomal alterations, androgen receptor, castration-resistant, inheritance, polymorphisms, oncogenes, metastasis, biomarkers, and immunotherapy.
Traditionally, androgen receptors (AR) have been the focus of research. Recently, identification of recurrent chromosomal alterations that lead to either multiplication of regions (gain-of-function) or deletion of regions (loss-of-function) has opened the door to greater genetic accessibility. These chromosomal aberrations lead to variation in copy number and gene expression. Some of these chromosomal alterations are inherited, while others undergo somatic mutations during disease progression. Inherited gene mutations that make one susceptible to prostate cancer have been identified with familial-linked studies. Somatic genes that progress tumorigenesis have also been identified. Research on the molecular biology of prostate cancer has characterized these genes into tumor suppressor genes or oncogenes. Additionally, genome-wide assay studies have identified many high-risk single-nucleotide polymorphisms recurrent throughout the prostate cancer-diagnosed genome. Castration-resistant prostate cancer is the most aggressive form of prostate cancer, and its research has elucidated many types of mutations associated with AR itself, including enhanced expression and amplification, point mutations, and alternative splicing. Understanding the molecular biology of prostate cancer has permitted more accurate identification using advanced biomarkers and therapy for aggressive forms using immunotherapy.
An age-related disease, prostate cancer commands profound attention. With increasing life expectancy and the continuous pursuit of it, prostate cancer is a powerful obstacle best defeated using targeted therapies specifically designed for the unique molecular profile of the malignancy.
在过去几十年中,随着对诊断、治疗和遗传学的不断深入理解,人们对前列腺癌诊断基因组有了更多的认识。
使用与前列腺癌遗传学相关的关键词变体(如染色体改变、雄激素受体、去势抵抗、遗传、多态性、癌基因、转移、生物标志物和免疫疗法)进行了全面的 MEDLINE® 和 Google Scholar 文献检索。
传统上,雄激素受体(AR)一直是研究的重点。最近,识别导致区域倍增(功能获得)或缺失(功能丧失)的反复染色体改变,为更大的遗传可及性打开了大门。这些染色体异常导致了拷贝数和基因表达的变化。这些染色体改变中的一些是遗传的,而另一些则在疾病进展过程中发生体细胞突变。通过家族连锁研究已经确定了使个体易患前列腺癌的遗传基因突变。也已经确定了促进肿瘤发生的体细胞基因。对前列腺癌分子生物学的研究将这些基因分为肿瘤抑制基因或癌基因。此外,全基因组检测研究还在前列腺癌诊断基因组中识别出许多高频单核苷酸多态性。去势抵抗性前列腺癌是最具侵袭性的前列腺癌形式,其研究阐明了与 AR 本身相关的许多突变类型,包括增强表达和扩增、点突变和选择性剪接。对前列腺癌分子生物学的理解允许使用先进的生物标志物更准确地识别,并使用免疫疗法针对侵袭性形式进行靶向治疗。
作为一种与年龄相关的疾病,前列腺癌引起了人们的极大关注。随着预期寿命的延长和对其的持续追求,前列腺癌是一个强大的障碍,最好使用专门针对恶性肿瘤独特分子特征设计的靶向疗法来战胜。