Chromosomal Basis of Adenocarcinoma of the Prostate

Abstract

Prostate cancer is the most frequent malignancy and the second leading cause of cancer deaths among males in the Western world. The clinical course of the disease is highly complex, and genetic factors underlying tumorigenesis are poorly understood. The challenge that lies ahead is to identify the important gene(s) that causes adenocarcinoma of the prostate. Chromosomal findings by cytogenetic and molecular methods, including Southern blotting, microsatellite analysis, fluorescence in situ hybridization, and comparative genomic hybridization, revealed a high frequency of chromosomal aberrations of heterogeneous nature, including: -1, +1, -1q, +4, -6q, -7, +7, -8, -8p, -8q, +i(8q), -9, -9p, -10, +10, +11, -12, -13q, -16, -16q, +16, -17, +17, +17q, -18, +18, -18q, +19p, +20q, +X, -Xq, -Y, and +Y. Specific chromosomal regions of alterations were 1q24-25, 2cen-q31, 5cen-q23.3, 6q14-23.2, 7q22-q31, 8p12-21, 8p22, 8q24-qter, 10q22.1, 10q23-25, 11p11.2, 16q24, 17p13.1, 18q12.2, and Xq11-12. Recently, a predisposing gene for early onset has been localized on 1q42.2-43. The losses of heterozygosity at specific chromosomal loci from chromosomes 5q, 6q, 7q, 8p, 8q, 10q, 13q, 16q, 17p, 17q, and 18q are generally correlated with poor prognosis in advanced tumor stage. In addition, an abnormal function of known tumor suppressor genes from these regions have been observed in prostate cancer. Although, the amplification of the androgen receptor gene at Xq11-13 and HER-2/neu gene at 17q11.2-q12 are novel findings, no single gene has been implicated in harboring prostate cancer. Frequent inactivation of PTEN/MMAC1 tumor suppressor gene at 10q23, MXI-1 at 10q25, KAI-1 at 11p11.2, Rb at 13q14.2, and p53 at 17p13.1 and deregulation of c-myc oncogene at 8q24 have recently been the subject of intense scrutiny and debate.

Differential expression of the mismatch repair gene hMSH2 in malignant prostate tissue is associated with cancer recurrence

“…Although several genetically altered regions have been described in prostate carcinoma, 3,4 the actual genes important for initiation and progression have not been clearly elucidated. Recent evidence suggests that several genetic loci may be linked to the hereditary form of this cancer, [5][6][7] and identification of these genes may provide insight into molecular pathogenesis of sporadic prostate carcinomas.…”

“…In addition, uncharacterized genes located on frequently deleted loci in sporadic prostate carcinoma could provide important clues in molecular pathogenesis of this malignancy. 3,4 Previously characterized cancer genes also have been investigated in prostate carcinoma, and a family of highly conserved genes involved in mismatch repair may play a role in pathogenesis.…”

Lenalidomide inhibits the malignant clone and up-regulates theSPARCgene mapping to the commonly deleted region in 5q− syndrome patients

“…Del(5q) also occurs in AML (20) and in several other cancers (21)(22)(23). The del(5q) aberration is associated with a favorable outcome when it occurs as an isolated cytogenetic aberration in low-risk MDS (5qϪ syndrome) (4,24).…”

Molecular biology of prostate cancer

“…43 This transcription factor is involved in differentiation and the level of C-MYC mRNA is higher in proliferating cells. 44 Levels fall dramatically when cells withdraw from the cell cycle or undergo terminal differentiation.…”