Allelotyping analysis at chromosome arm 8p of high‐grade prostatic intraepithelial neoplasia and incidental, latent, and clinical prostate cancers

Abstract

In this study, we used 7 informative microsatellite markers at 8p22, 23.1, and 23.2 in Japanese patients to compare frequency of loss of heterozygosity (LOH) in 53 lesions of high-grade prostatic intraepithelial neoplasia (HGPIN), 38 cases (38 lesions) of incidental prostate cancer (IPC), 31 cases (41 lesions) of latent prostate cancer (LPC), and 102 cases (168 lesions) of clinical prostate cancer (CPC). The frequency of LOH at 8p22-23.2 with at least 1 marker was 0%, 33%, 57%, and 51% in the HGPIN, IPC, LPC, and CPC cases, respectively. No statistically significant difference was found at 8p22-23.2 between the types of prostate cancer. However, the frequency of 8p22 deletion was significantly higher in CPC and LPC cases than in IPC cases (P = 0.0003) or lesions (P = 0.0017). The frequency of LOH at 8p22 and 8p23.1 loci in high-grade tumors was significantly higher than in low-grade tumors in both the LPCs/IPCs and CPCs (P < 0.05). Allelic loss at 8p22 was significantly more frequent in CPC than in IPC (P = 0.002) and in pT4 CPC than in earlier-stage CPC (P = 0.038). These findings suggest that deletion of 8p is an important event in both the initiation and metastasis of prostate cancer. The extremely high frequency of LOH at 8p22-23.1 in high-grade tumors suggests the existence of a novel putative tumor-suppressor gene associated with the progression of prostate cancer. These results should be useful in identifying the target gene of deletion at 8p.

Deletion at chromosome arms 6q16–22 and 10q22.3–23.1 associated with initiation of prostate cancer

“…Previously, we had performed a genome-wide search for LOH with human genetic markers in several types of cancer and confirmed that chromosomal alterations, especially deletions of some restricted regions, such as 8p22-23.1 and 13q14, are not only related with the initiation but also closely associated with subsequent progression of human cancers, especially in the metastasis of primary tumors. 21,22 The LOH at 6q16-22 and 10q22.3-23.1 tended to differ from the results of our previous allelotyping at 8p and 13q in the same samples.…”

“…The LOH at 6q16-22 and 10q22.3-23.1 tended to differ from the results of our previous allelotyping at 8p and 13q in the same samples and another type of human cancer. [21][22][23][24] These results led us to suggest that LOH at 6q16-22 and 10q22.3-23.1 might not be a newly occurring genetic change during the progression from early stage prostate cancer to clinical significant prostate cancer even in the metastatic stage. Previously, we had performed a genome-wide search for LOH with human genetic markers in several types of cancer and confirmed that chromosomal alterations, especially deletions of some restricted regions, such as 8p22-23.1 and 13q14, are not only related with the initiation but also closely associated with subsequent progression of human cancers, especially in the metastasis of primary tumors.…”

“…The tumor volumes of the IPCs were measured as previously reported. 21,22 All specimens were formalin-fixed and paraffin-embedded tissues were processed with routine histological methods. Use of the tissues was approved by the ethics committee of the Jikei University School of Medicine before the study.…”

“…Following a standard series of phenol/chloroform extractions, DNA samples were prepared. 21,22 Matched tumors, HGPINs and normal specimens from IPCs and CPCs were analyzed for LOH by amplification of polymorphic microsatellite markers using the polymerase chain reaction (PCR). Eleven microsatellite markers at 6q16-22 and 10q22.3-23.1 were used.…”

Genetic and epigenetic silencing of SCARA5 may contribute to human hepatocellular carcinoma by activating FAK signaling

“…In addition to HCC, the LOH on chromosome 8p has been implicated in other human cancers, including bladder cancer (27), breast cancer (28,29), B cell lymphoma (30), prostate cancer (31,32), and head and neck squamous cell carcinoma (33). Thus, the identification of candidate tumor suppressor genes on chromosome 8p and elucidation of their biological functions would be a significant advance in our understanding of tumorigenesis and progression.…”