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A candidate metastasis-associated DNA marker for ductal mammary carcinoma.

Achary PM, Zhao H, Fan Z, Gogineni S, Pulijaal VR, Herbst L, Mahadevia PS, Jones JG, Klinger HP, Vikram B - Breast Cancer Res. (2003)

Bottom Line: Representational difference analysis products yielded 10 unique metastasis-associated DNA sequences (MADS), i.e. products apparently lost in metastatic cell DNA.PCR screening of three additional breast carcinoma cell lines with known losses in specific chromosomal regions also showed the presence of MADS-IX.These data suggest that MADS-IX possibly is part of a novel candidate metastasis-associated gene located close to the PTEN gene on chromosome 10q.

View Article: PubMed Central - HTML - PubMed

Affiliation: Metastasis Laboratory, Department of Radiation Oncology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA. achary@aecom.yu.edu

ABSTRACT

Background: Molecular genetic markers to identify the 13% lymph node-negative mammary carcinomas that are prone to develop metastases would clearly be of considerable value in indicating those cases in need of early aggressive therapy.

Methods: Representational difference analysis was used in an attempt to identify genetic alterations related to breast cancer metastasis by comparing genomic DNA from microdissected normal cells and from metastatic cells of ductal breast carcinoma patients.

Results: Representational difference analysis products yielded 10 unique metastasis-associated DNA sequences (MADS), i.e. products apparently lost in metastatic cell DNA. Of these sequences, MADS-IX was found to be lost in the transition from primary to metastasis in two out of five ductal breast carcinoma cases. This sequence was localized on chromosome 10q21 by radiation hybrid mapping and fluorescence in situ hybridization. The PTEN gene, which is also located on chromosome 10q, was detected to be present by PCR in all five cases. On the contrary, a breast carcinoma cell line, HCC-1937, which has homozygous loss of a region encompassing the PTEN gene, showed the presence of MADS-IX. PCR screening of three additional breast carcinoma cell lines with known losses in specific chromosomal regions also showed the presence of MADS-IX.

Conclusion: These data suggest that MADS-IX possibly is part of a novel candidate metastasis-associated gene located close to the PTEN gene on chromosome 10q. The first set of PCR screening in five patient samples indicates that it could be used as a molecular marker for ductal mammary metastasis.

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Related in: MedlinePlus

PCR screening of MADS-IX and PTEN on DNA samples from four tumor cell lines and matched normal DNA. Results (first row) show that MADS-IX is present in all the tumor cell lines (HCC-1806, HCC-1143, HCC-1428 and HCC-1937) especially the HCC-1937 cell line, which has loss of a region encompassing the PTEN gene. Screening of PTEN in these four cell lines (second row) show its presence in the HCC-1806, HCC-1143 and HCC-1428 tumor cell lines but, as expected, it is missing in HCC-1937. β-Actin was used as an internal control.
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Figure 5: PCR screening of MADS-IX and PTEN on DNA samples from four tumor cell lines and matched normal DNA. Results (first row) show that MADS-IX is present in all the tumor cell lines (HCC-1806, HCC-1143, HCC-1428 and HCC-1937) especially the HCC-1937 cell line, which has loss of a region encompassing the PTEN gene. Screening of PTEN in these four cell lines (second row) show its presence in the HCC-1806, HCC-1143 and HCC-1428 tumor cell lines but, as expected, it is missing in HCC-1937. β-Actin was used as an internal control.

Mentions: Second, MADS-IX and PTEN were screened in four breast tumor cell lines (HCC-1806, HCC-1143, HCC-1428 and HCC-1937) and matched normal DNA. The first three tumor cell lines had known losses in specific chromosomal regions, and the fourth had loss of homozygosity of the PTEN gene. PCR screening of MADS-IX and PTEN showed that MADS-IX is present in all four tumor cell lines, but PTEN is only present in cell lines HCC-1806, HCC-1143 and HCC-1428 and is missing in HCC-1937 (Fig. 5).


A candidate metastasis-associated DNA marker for ductal mammary carcinoma.

Achary PM, Zhao H, Fan Z, Gogineni S, Pulijaal VR, Herbst L, Mahadevia PS, Jones JG, Klinger HP, Vikram B - Breast Cancer Res. (2003)

PCR screening of MADS-IX and PTEN on DNA samples from four tumor cell lines and matched normal DNA. Results (first row) show that MADS-IX is present in all the tumor cell lines (HCC-1806, HCC-1143, HCC-1428 and HCC-1937) especially the HCC-1937 cell line, which has loss of a region encompassing the PTEN gene. Screening of PTEN in these four cell lines (second row) show its presence in the HCC-1806, HCC-1143 and HCC-1428 tumor cell lines but, as expected, it is missing in HCC-1937. β-Actin was used as an internal control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC154149&req=5

Figure 5: PCR screening of MADS-IX and PTEN on DNA samples from four tumor cell lines and matched normal DNA. Results (first row) show that MADS-IX is present in all the tumor cell lines (HCC-1806, HCC-1143, HCC-1428 and HCC-1937) especially the HCC-1937 cell line, which has loss of a region encompassing the PTEN gene. Screening of PTEN in these four cell lines (second row) show its presence in the HCC-1806, HCC-1143 and HCC-1428 tumor cell lines but, as expected, it is missing in HCC-1937. β-Actin was used as an internal control.
Mentions: Second, MADS-IX and PTEN were screened in four breast tumor cell lines (HCC-1806, HCC-1143, HCC-1428 and HCC-1937) and matched normal DNA. The first three tumor cell lines had known losses in specific chromosomal regions, and the fourth had loss of homozygosity of the PTEN gene. PCR screening of MADS-IX and PTEN showed that MADS-IX is present in all four tumor cell lines, but PTEN is only present in cell lines HCC-1806, HCC-1143 and HCC-1428 and is missing in HCC-1937 (Fig. 5).

Bottom Line: Representational difference analysis products yielded 10 unique metastasis-associated DNA sequences (MADS), i.e. products apparently lost in metastatic cell DNA.PCR screening of three additional breast carcinoma cell lines with known losses in specific chromosomal regions also showed the presence of MADS-IX.These data suggest that MADS-IX possibly is part of a novel candidate metastasis-associated gene located close to the PTEN gene on chromosome 10q.

View Article: PubMed Central - HTML - PubMed

Affiliation: Metastasis Laboratory, Department of Radiation Oncology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA. achary@aecom.yu.edu

ABSTRACT

Background: Molecular genetic markers to identify the 13% lymph node-negative mammary carcinomas that are prone to develop metastases would clearly be of considerable value in indicating those cases in need of early aggressive therapy.

Methods: Representational difference analysis was used in an attempt to identify genetic alterations related to breast cancer metastasis by comparing genomic DNA from microdissected normal cells and from metastatic cells of ductal breast carcinoma patients.

Results: Representational difference analysis products yielded 10 unique metastasis-associated DNA sequences (MADS), i.e. products apparently lost in metastatic cell DNA. Of these sequences, MADS-IX was found to be lost in the transition from primary to metastasis in two out of five ductal breast carcinoma cases. This sequence was localized on chromosome 10q21 by radiation hybrid mapping and fluorescence in situ hybridization. The PTEN gene, which is also located on chromosome 10q, was detected to be present by PCR in all five cases. On the contrary, a breast carcinoma cell line, HCC-1937, which has homozygous loss of a region encompassing the PTEN gene, showed the presence of MADS-IX. PCR screening of three additional breast carcinoma cell lines with known losses in specific chromosomal regions also showed the presence of MADS-IX.

Conclusion: These data suggest that MADS-IX possibly is part of a novel candidate metastasis-associated gene located close to the PTEN gene on chromosome 10q. The first set of PCR screening in five patient samples indicates that it could be used as a molecular marker for ductal mammary metastasis.

Show MeSH
Related in: MedlinePlus