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Allelic loss on chromosome band 18p11.3 occurs early and reveals heterogeneity in breast cancer progression.

Kittiniyom K, Gorse KM, Dalbegue F, Lichy JH, Taubenberger JK, Newsham IF - Breast Cancer Res. (2001)

Bottom Line: Significant loss of heterozygosity (LOH) (63%) was found, with 56% occurring early in ductal carcinoma in situ.When compared with other LOH data, 18p LOH was found in conjunction with allelic deletion on 3p, 9p, 17p and 17q, while 13q, 16q, and 11p were less frequently associated.These analyses suggest chromosome 18p11 alteration is a common and early event in breast disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Virginia Commonweath University, Richmond, USA.

ABSTRACT
We examined the stage specificity and heterogeneity of 18p11 alterations in a series of tumors representing 96 microdissected samples. Significant loss of heterozygosity (LOH) (63%) was found, with 56% occurring early in ductal carcinoma in situ. Although most cases indicated LOH was clonally inherited, heterogeneity for 18p LOH occurred in 27% of tumors. When compared with other LOH data, 18p LOH was found in conjunction with allelic deletion on 3p, 9p, 17p and 17q, while 13q, 16q, and 11p were less frequently associated. These analyses suggest chromosome 18p11 alteration is a common and early event in breast disease.

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Heterogeneity for LOH on chromosome 18p in breast cancer progression. Schematic diagrams show the different patterns of progression based on this chromosome 18p study. Nine cases show clonal progression where 18p LOH occurs either in DCIS or IDC and is clonally inherited in related later stages of tumor progression. Two cases show LOH first appearing in the metastatic stage. In contrast, four cases show heterogeneity for alterations on 18p. Two specimens show LOH in the DCIS component but not in the associated IDC component. The other cases show the presence of microsatellite instability in earlier but not later stage disease.
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Figure 2: Heterogeneity for LOH on chromosome 18p in breast cancer progression. Schematic diagrams show the different patterns of progression based on this chromosome 18p study. Nine cases show clonal progression where 18p LOH occurs either in DCIS or IDC and is clonally inherited in related later stages of tumor progression. Two cases show LOH first appearing in the metastatic stage. In contrast, four cases show heterogeneity for alterations on 18p. Two specimens show LOH in the DCIS component but not in the associated IDC component. The other cases show the presence of microsatellite instability in earlier but not later stage disease.

Mentions: We also examined the extent of heterogeneity associated with chromosome 18p LOH (Fig. 2). In tumors where information was attainable for two or more disease stages, 73% (11/15) displayed a pattern of classic clonal progression. LOH first appeared in the DCIS stage for the majority. Four tumors (27%) were, however, interestingly identified with genetic heterogeneity for chromosome 18p events where DCIS-identified events were not found in associated invasive foci. Genetic events involving chromosome 18p sequences thus do not follow a classic progression paradigm in 27% of tumor cases analyzed as part of this study.


Allelic loss on chromosome band 18p11.3 occurs early and reveals heterogeneity in breast cancer progression.

Kittiniyom K, Gorse KM, Dalbegue F, Lichy JH, Taubenberger JK, Newsham IF - Breast Cancer Res. (2001)

Heterogeneity for LOH on chromosome 18p in breast cancer progression. Schematic diagrams show the different patterns of progression based on this chromosome 18p study. Nine cases show clonal progression where 18p LOH occurs either in DCIS or IDC and is clonally inherited in related later stages of tumor progression. Two cases show LOH first appearing in the metastatic stage. In contrast, four cases show heterogeneity for alterations on 18p. Two specimens show LOH in the DCIS component but not in the associated IDC component. The other cases show the presence of microsatellite instability in earlier but not later stage disease.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC30703&req=5

Figure 2: Heterogeneity for LOH on chromosome 18p in breast cancer progression. Schematic diagrams show the different patterns of progression based on this chromosome 18p study. Nine cases show clonal progression where 18p LOH occurs either in DCIS or IDC and is clonally inherited in related later stages of tumor progression. Two cases show LOH first appearing in the metastatic stage. In contrast, four cases show heterogeneity for alterations on 18p. Two specimens show LOH in the DCIS component but not in the associated IDC component. The other cases show the presence of microsatellite instability in earlier but not later stage disease.
Mentions: We also examined the extent of heterogeneity associated with chromosome 18p LOH (Fig. 2). In tumors where information was attainable for two or more disease stages, 73% (11/15) displayed a pattern of classic clonal progression. LOH first appeared in the DCIS stage for the majority. Four tumors (27%) were, however, interestingly identified with genetic heterogeneity for chromosome 18p events where DCIS-identified events were not found in associated invasive foci. Genetic events involving chromosome 18p sequences thus do not follow a classic progression paradigm in 27% of tumor cases analyzed as part of this study.

Bottom Line: Significant loss of heterozygosity (LOH) (63%) was found, with 56% occurring early in ductal carcinoma in situ.When compared with other LOH data, 18p LOH was found in conjunction with allelic deletion on 3p, 9p, 17p and 17q, while 13q, 16q, and 11p were less frequently associated.These analyses suggest chromosome 18p11 alteration is a common and early event in breast disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Virginia Commonweath University, Richmond, USA.

ABSTRACT
We examined the stage specificity and heterogeneity of 18p11 alterations in a series of tumors representing 96 microdissected samples. Significant loss of heterozygosity (LOH) (63%) was found, with 56% occurring early in ductal carcinoma in situ. Although most cases indicated LOH was clonally inherited, heterogeneity for 18p LOH occurred in 27% of tumors. When compared with other LOH data, 18p LOH was found in conjunction with allelic deletion on 3p, 9p, 17p and 17q, while 13q, 16q, and 11p were less frequently associated. These analyses suggest chromosome 18p11 alteration is a common and early event in breast disease.

Show MeSH
Related in: MedlinePlus