Allelic losses at loci on chromosome 10 are associated with metastasis and progression of human prostate cancer

Abstract

DNA samples from tumors and paired normal tissues from 48 patients with prostate cancer (stage B, 16 cases; stage C, 14 cases; stage D, 18 cases) were examined with 26 polymorphic markers spanning chromosome 10. Allelic losses were observed in 17 of the 46 cases (37%) that were informative with at least one of the markers. Detailed deletion mapping identified two distict commonly deleted regions on the long arm of chromosome 10 (10q22-q24:7 cM and 10q25.1:17 cM) and one on 10p, suggesting that at least three tumor suppressor genes associated with prostate cancer are present on this chromosome. We observed loss of heterozygosity more frequently in tumors from fatal cases (stage D, 8/16, 50%) than in localized tumors (stage B, 0/16, 0%; P = 0.001 or stage B + C, 5/30, 17%; P = 0.02 Fisher's exact test). All metastatic tissues showed allelic loss at one or more loci on 10q. In five of the nine patients from whom DNAs were available from both metastatic and primary tumors, the primary cancer foci had no detectable abnormality of chromosome 10, while the metastatic foci showed allelic loss on chromosome 10. These results suggested that inactivation of one or more tumor suppressor genes on chromosome 10 plays an important role in late stages of prostate cancer.

Secretory Lipophilins: A Tale of Two Species

“…21 Both mammaglobin and lipophilin C (mammaglobin B) show considerable promise as markers for detecting micrometastatic cancer lesions in the lymph nodes and bone marrow. 23,24 The chromosomal proximity of the lipophilin C, mammaglobin, and uteroglobin genes strongly suggests that all three genes evolved by repeated duplications of a common precursor.…”

“…Lipophilin B resides on chromosome 23, in a region of considerable interest. Not only does chromosome 10q22–23 harbor an anti‐oncogene strongly implicated in prostate cancer, 24 it has also been implicated in Cowden syndrome, an autosomal dominant hamartoma syndrome associated with a high risk of thyroid and breast cancer. 25,26 Although interest has justifiably centered on PTEN/MMAC1, evidence suggests that additional prostatic cancer tumor suppressor genes may be situated close to the PTEN/MMAC1 locus on 10q23.…”

Neuroendocrine differentiation in the progression of prostate cancer

“…Prostate cancer (PCa) is a leading cause of cancer deaths in Western countries and its incidence is also among the most rapidly increasing cancers in Japanese men. Many clinical, endocrinological, pathological, and genetic prognostic factors have been used for the management of PCa 1–6 . Understanding these factors will help to individualize PCa.…”

Infrequent genetic alterations of the tumor suppressor gene PTEN/MMAC1 in squamous cell carcinoma of the oral cavity

“…It has been suggested that PTEN/MMAC1 is involved in the metastasis process. In addition to the observation of 10q abnormalities and allelic loss in metastatic tumors (15, 17–20) Petersen et al . (21) recently showed that loss of heterozygosity on chromosome 10q is associated with the metastatic phenotype of squamous cell carcinomas of the lung.…”