Pathology and genetics of tumours of the urinary system and male genital organs

It is increasingly evident that many of the genomic mutations in cancer reside inside regions that do not encode proteins. However, these regions are often transcribed into long noncoding RNAs (lncRNAs). The recent application of next-generation sequencing to a growing number of cancer transcriptomes has indeed revealed thousands of lncRNAs whose aberrant expression is associated with different cancer types. Among the few that have been functionally characterized, several have been linked to malignant transformation. Notably, these lncRNAs have key roles in gene regulation and thus affect various aspects of cellular homeostasis, including proliferation, survival, migration or genomic stability. This review aims to summarize current knowledge of lncRNAs from the cancer perspective. It discusses the strategies that led to the identification of cancer-related lncRNAs and the methodologies and challenges involving the study of these molecules, as well as the imminent applications of these findings to the clinic.

The emerging role of lncRNAs in cancer

BACKGROUND: In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now repo ...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa043739

Radical prostatectomy versus watchful waiting in early prostate cancer.

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 x 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 x 10(-9)), ANK3 (rs10994359, P = 2.5 x 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10(-9)).

/pdf/genome-wide-association-study-identifies-five-new-4krd06ut6d.pdf

Genome-wide association study identifies five new schizophrenia loci

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(04)16044-3.pdf

Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis

Histological Classification of Urinary Bladder Tumours.- Definitions and Explanatory Notes.- Epithelial Tumours of the Bladder.- Non-epithelial Tumours.- Miscellaneous Tumours.- Metastatic Tumours and Secondary Extensions.- Unclassified Tumours.- Epithelial Abnormalities.- Tumour-like Lesions.- TNM Classification of Tumours of the Urinary Bladder.- Illustrations.

Histological Typing of Urinary Bladder Tumours

Tumors of the male genital system

Over the last 22 years, we have encountered 34 examples of a highly aggressive neoplasm with a microscopic morphology that is highly predictive of finding sickled erythrocytes in the tissue. With the exception of one patient, all are believed to have had sickle cell trait or, in one case, hemoglobin

Renal medullary carcinoma. The seventh sickle cell nephropathy.

In a study of 208 total prostates removed surgically for early carcinoma of the prostate and studied by the step-section technique, we found that 97% were located either peripherally or both peripherally and centrally; 80% were bilateral, and 85% were multifocal. In most of the cases, the tumor was actually more extensive than detected by rectal examination, but there was reasonable agreement (74.5%) between the urologist and pathologist in assessing the presence of local extension of carcinoma. Evaluation of various factors affecting survival and mortality disclosed that an extension of the tumor to seminal vesicles or invasion of the capsule, whether detected clinically or pathologically, had an unfavorable prognosis while the side involved, the location of the tumor, and perineural invasion had no significant effect on the prognosis.

Carcinoma of the prostate: Prognostic evaluation of certain pathologic features in 208 radical prostatectomies

Observations on 6,000 testicular tumors revealed the following: Testicular tumors constitute the fourth most common cause of deaths from neoplasia in the age group of 15–34 years of age. There is a definite geographic, racial, and age distribution. The cause of testicular tumors is unknown, but cryptorchidism, trauma, infections, and genetic and endocrine factors appear to play a role in their development. Germ cell tumors comprise the large majority of testicular tumors and present one or more of 4 bask histologic patterns: seminoma, embryonal carcinoma, choriocarcinoma, and teratoma. In 40% the tumors show admixtures of 2 or more of these basic cell types. Tumors of specialized gonadal stroma constitute about 6% of testicular tumors and consist of Leydig cell, Sertoli cell, and granulosa-theca cell tumors, or admixtures of these. The most important metastatic tumor of the testes is malignant lymphoma, initially manifested as testicular tumor.

F. K. Mostofi

Papers

Histological Typing of Urinary Bladder Tumours

Tumors of the male genital system

Renal medullary carcinoma. The seventh sickle cell nephropathy.

Carcinoma of the prostate: Prognostic evaluation of certain pathologic features in 208 radical prostatectomies

Testicular tumors. Epidemiologic, etiologic, and pathologic features