Integration of Somatic Deletion Analysis of Prostate Cancers and Germline Linkage Analysis of Prostate Cancer Families Reveals Two Small Consensus Regions for Prostate Cancer Genes at 8p

Abstract

The evidence for tumor suppressor genes at 8p is well supported by many somatic deletion studies and genetic linkage studies. However, it remains a challenge to pinpoint the tumor suppressor genes at 8p primarily because the implicated regions are broad. In this study, we attempted to narrow down the implicated regions by incorporating evidence from both somatic and germline studies. Using high-resolution Affymetrix arrays, we identified two small common deleted regions among 55 prostate tumors at 8p23.1 (9.8-11.5 Mb) and 8p21.3 (20.6-23.7 Mb). Interestingly, our fine mapping linkage analysis at 8p among 206 hereditary prostate cancer families also provided evidence for linkage at these two regions at 8p23.1 (5.8-11.2 Mb) and at 8p21.3 (19.6-23.9 Mb). More importantly, by combining the results from the somatic deletion analysis and genetic linkage analysis, we were able to further narrow the regions to f1.4 Mb at 8p23.1 and f3.1 Mb at 8p21.3. These smaller consensus regions may facilitate a more effective search for prostate cancer genes at 8p. [Cancer Res 2007;67(9):4098-103]

Suppression of SOX7 by DNA methylation and its tumor suppressor function in acute myeloid leukemia

“…21 In prostate cancer, deletion was found in ;50% of cases at the short arm of chromosome 8 (8p23.1) where SOX7 gene normally resides. 22 In this study, we examined the hitherto unknown expression pattern, regulation, and pathogenetic mechanism of SOX7 in human myeloid malignancies. SOX7 gene was uniquely silenced in myeloid malignancies due to promoter methylation.…”

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.…”

Bin3 Deletion Causes Cataracts and Increased Susceptibility to Lymphoma during Aging

“…studies of the 8p21.3 region have highlighted a f1 Mb region containing f10 genes, including the Bin3 gene, as a focal point of relevance to non-Hodgkin's lymphoma and prostate adenocarcinoma (11)(12)(13). The appearance of lymphomas in Bin3 À/À mice is clearly consistent with the possible relevance of Bin3 as a tumor suppressor in this setting.…”

“…Although the identity of these genes has yet to be identified conclusively, inactivation of one or more is strongly implicated in the genesis of a variety of epithelial and hematologic malignancies. In particular, there is extensive evidence pointing to a suppressor locus 8p21.3 that is germane to the development of non-Hodgkin's lymphoma (11), prostate cancer (12,(45)(46)(47)(48), head, neck, oral, and laryngeal cancers (13,49), and lung cancers (50). Indeed, recent fine-mapping Figure 6.…”

“…Indeed, losses of chromosome 8p represent one of the most common events in epithelial tumors and B lymphomas and such events have been associated strongly with progression in advanced metastatic disease. In particular, recent fine-mapping studies have highlighted a f1 Mb region at 8p21.3, including Bin3, as the site of a tumor suppressor gene(s) involved in the development of non-Hodgkin's lymphoma, head and neck cancer, and prostate adenocarcinoma (11)(12)(13). However, among the genes within the region implicated, a clear suppressor has yet to been identified.…”