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. 2002 Sep-Oct;4(5):424-31.
doi: 10.1038/sj.neo.7900254.

Prostate cancer aggressiveness locus on chromosome 7q32-q33 identified by linkage and allelic imbalance studies

Phillippa J Neville  1 , David V Conti, Pamela L Paris, Howard Levin, William J Catalona, Brian K Suarez, John S Witte, Graham Casey
Affiliations

Prostate cancer aggressiveness locus on chromosome 7q32-q33 identified by linkage and allelic imbalance studies

Phillippa J Neville et al. Neoplasia. 2002 Sep-Oct.

Abstract

The biologic aggressiveness of prostate tumors is an important indicator of prognosis. Chromosome 7q32-q33 was recently reported to show linkage to more aggressive prostate cancer, based on Gleason score, in a large sibling pair study. We report confirmation and narrowing of the linked region using finer-scale genotyping. We also report a high frequency of allelic imbalance (AI) defined within this locus in a series of 48 primary prostate tumors from men unselected for family history or disease status. The highest frequency of AI was observed with adjacent markers D7S2531 (52%) and D7S1804 (36%). These two markers delineated a common region of AI, with 24 tumors exhibiting interstitial AI involving one or both markers. The 1.1-Mb candidate region contains relatively few transcripts. Additionally, we observed positive associations between interstitial AI at D7S1804 and early age at diagnosis (P=.03) as well as a high combined Gleason score and tumor stage (P=.06). Interstitial AI at D7S2531 was associated with a positive family history of prostate cancer (P=.05). These data imply that we have localized a prostate cancer tumor aggressiveness loci to chromosome 7q32-q33 that is involved in familial and nonfamilial forms of prostate cancer.

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Figures

Figure 1
Figure 1
Results from linkage analysis of prostate cancer aggressiveness on chromosome 7. Broken lines indicate results from the original analysis; solid line denotes results from new analysis. Values on the x-axis show marker positions according to Marshfield Medical Research Foundation, Human Genetics web site and our radiation hybrid mapping data.
Figure 2
Figure 2
Summary of 24 primary prostate tumor samples showing interstitial AI on 7q involving D7S2531 and D7S1804. Markers are listed on the left; sample numbers are shown across the top. (□) Informative samples with no AI; (■) informative samples demonstrating AI; (⊖) noninformative (homozygous) samples; (—) did not work. Boxes define maximum extent of AI for each sample.
Figure 3
Figure 3
Examples of autoradiographs from AI studies on matched normal (N) and prostate tumor (T) pairs. Samples 7-286 and 7-393 both exhibit AI at markers D7S2531 and D7S1804 but retain D7S2519 and D7S2452. Tumor 7-220 shows AI at D7S2531 but no AI at any neighboring marker. Sample 7-310 demonstrates AI at D7S1804 but not at any flanking marker. (■) AI; (□) no AI; arrows indicate AI.
Figure 4
Figure 4
Schematic representation of 7q32-q33 region showing positions of linked region, AI, fragile site and ST7 tumor suppressor gene. Not shown to scale. ST7=supression of tumorigenicity 7 gene; FRA7H=fragile site 7H; AI=common region of allelic imbalance.
See this image and copyright information in PMC

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