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Identification of two contiguous minimally deleted regions on chromosome 1p36.31-p36.32 in oligodendroglial tumours.

Dong Z, Pang JS, Ng MH, Poon WS, Zhou L, Ng HK - Br. J. Cancer (2004)

Bottom Line: The small overlapping intervals facilitated the delineation of two contiguous minimally deleted regions of 0.76 Mb, defined by D1S468 and D1S2845, and of 0.41 Mb, bound by D1S2893 and D1S1608, on 1p36.31-36.32.Based on current reference human genome sequence these deletion regions have been sequenced almost to entirety and contain eight annotated genes.TP73, DFFB and SHREW1 are the only known genes located in these deletion regions, while the others are uncharacterised novel genes.

View Article: PubMed Central - PubMed

Affiliation: 1Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.

ABSTRACT
Loss of the short arm of chromosome 1 is a hallmark of oligodendroglial tumours (OTs). Deletion mapping studies in OTs have revealed multiple commonly deleted regions on chromosome 1p, suggesting that there are more than one tumour suppressor gene. To map critical deletion regions on 1p, a series of 25 OTs were examined for loss of heterozygosity (LOH) on 19 polymorphic markers across the 1p arm using microsatellite analysis. Our study revealed that 60% of tumours had LOH of all informative markers on 1p and identified one tumour showing LOH at telomeric markers only. Since this deletion region lies in one of the critical deletion intervals defined previously, we then screened another series of 27 OTs specifically at 1p36.3 for LOH using nine polymorphic markers. A total of 12% (six out of 52) of tumours were found to carry interstitial deletions. The allelic status and the deletion breakpoints in these tumours with interstitial deletion were further verified by fluorescent in situ hybridisation. The small overlapping intervals facilitated the delineation of two contiguous minimally deleted regions of 0.76 Mb, defined by D1S468 and D1S2845, and of 0.41 Mb, bound by D1S2893 and D1S1608, on 1p36.31-36.32. Based on current reference human genome sequence these deletion regions have been sequenced almost to entirety and contain eight annotated genes. TP73, DFFB and SHREW1 are the only known genes located in these deletion regions, while the others are uncharacterised novel genes. In conclusion, our study has narrowed down the critical tumour suppressor loci on 1p36.3, in which two minimally deleted regions are mapped, and markedly reduced the number of candidate genes to be screened for their involvement in OT development.

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Related in: MedlinePlus

Representative results of microsatellite and interphase FISH analyses of case A18. Microsatellite markers are indicated on left with corresponding BAC or PAC clones containing such markers in parentheses. Concordant results are obtained for both techniques. Of note is that FISH reveals allelic loss at the noninformative locus D1S2660. Allelic loss (AL) in microsatellite analysis is indicated by arrowhead and is represented by one red (target) signal and two green (chromosome 1 centromere) signals in FISH. Allelic retention (AR) is indicated by the presence of both alleles in microsatellite analysis and is represented by two red and two green signals. T=tumour; B=tumour-matched blood.
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fig3: Representative results of microsatellite and interphase FISH analyses of case A18. Microsatellite markers are indicated on left with corresponding BAC or PAC clones containing such markers in parentheses. Concordant results are obtained for both techniques. Of note is that FISH reveals allelic loss at the noninformative locus D1S2660. Allelic loss (AL) in microsatellite analysis is indicated by arrowhead and is represented by one red (target) signal and two green (chromosome 1 centromere) signals in FISH. Allelic retention (AR) is indicated by the presence of both alleles in microsatellite analysis and is represented by two red and two green signals. T=tumour; B=tumour-matched blood.

Mentions: We then employed an independent assay, interphase FISH, to verify the allelic status and to determine the deletion breakpoints in tumours that showed interstitial deletion. Four cases (A18, A19, B9 and B14), for which tissues were available, were subjected to FISH. Representative results of FISH are shown in Figure 3Figure 3


Identification of two contiguous minimally deleted regions on chromosome 1p36.31-p36.32 in oligodendroglial tumours.

Dong Z, Pang JS, Ng MH, Poon WS, Zhou L, Ng HK - Br. J. Cancer (2004)

Representative results of microsatellite and interphase FISH analyses of case A18. Microsatellite markers are indicated on left with corresponding BAC or PAC clones containing such markers in parentheses. Concordant results are obtained for both techniques. Of note is that FISH reveals allelic loss at the noninformative locus D1S2660. Allelic loss (AL) in microsatellite analysis is indicated by arrowhead and is represented by one red (target) signal and two green (chromosome 1 centromere) signals in FISH. Allelic retention (AR) is indicated by the presence of both alleles in microsatellite analysis and is represented by two red and two green signals. T=tumour; B=tumour-matched blood.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747719&req=5

fig3: Representative results of microsatellite and interphase FISH analyses of case A18. Microsatellite markers are indicated on left with corresponding BAC or PAC clones containing such markers in parentheses. Concordant results are obtained for both techniques. Of note is that FISH reveals allelic loss at the noninformative locus D1S2660. Allelic loss (AL) in microsatellite analysis is indicated by arrowhead and is represented by one red (target) signal and two green (chromosome 1 centromere) signals in FISH. Allelic retention (AR) is indicated by the presence of both alleles in microsatellite analysis and is represented by two red and two green signals. T=tumour; B=tumour-matched blood.
Mentions: We then employed an independent assay, interphase FISH, to verify the allelic status and to determine the deletion breakpoints in tumours that showed interstitial deletion. Four cases (A18, A19, B9 and B14), for which tissues were available, were subjected to FISH. Representative results of FISH are shown in Figure 3Figure 3

Bottom Line: The small overlapping intervals facilitated the delineation of two contiguous minimally deleted regions of 0.76 Mb, defined by D1S468 and D1S2845, and of 0.41 Mb, bound by D1S2893 and D1S1608, on 1p36.31-36.32.Based on current reference human genome sequence these deletion regions have been sequenced almost to entirety and contain eight annotated genes.TP73, DFFB and SHREW1 are the only known genes located in these deletion regions, while the others are uncharacterised novel genes.

View Article: PubMed Central - PubMed

Affiliation: 1Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.

ABSTRACT
Loss of the short arm of chromosome 1 is a hallmark of oligodendroglial tumours (OTs). Deletion mapping studies in OTs have revealed multiple commonly deleted regions on chromosome 1p, suggesting that there are more than one tumour suppressor gene. To map critical deletion regions on 1p, a series of 25 OTs were examined for loss of heterozygosity (LOH) on 19 polymorphic markers across the 1p arm using microsatellite analysis. Our study revealed that 60% of tumours had LOH of all informative markers on 1p and identified one tumour showing LOH at telomeric markers only. Since this deletion region lies in one of the critical deletion intervals defined previously, we then screened another series of 27 OTs specifically at 1p36.3 for LOH using nine polymorphic markers. A total of 12% (six out of 52) of tumours were found to carry interstitial deletions. The allelic status and the deletion breakpoints in these tumours with interstitial deletion were further verified by fluorescent in situ hybridisation. The small overlapping intervals facilitated the delineation of two contiguous minimally deleted regions of 0.76 Mb, defined by D1S468 and D1S2845, and of 0.41 Mb, bound by D1S2893 and D1S1608, on 1p36.31-36.32. Based on current reference human genome sequence these deletion regions have been sequenced almost to entirety and contain eight annotated genes. TP73, DFFB and SHREW1 are the only known genes located in these deletion regions, while the others are uncharacterised novel genes. In conclusion, our study has narrowed down the critical tumour suppressor loci on 1p36.3, in which two minimally deleted regions are mapped, and markedly reduced the number of candidate genes to be screened for their involvement in OT development.

Show MeSH
Related in: MedlinePlus