Publications (3)6.78 Total impact
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ABSTRACT: The estrogen receptor (ER) is a well-known predictor of breast cancer response to endocrine therapy. ER+ progesterone receptor (PR)- breast tumors have a poorer response to endocrine therapy and a more aggressive phenotype than ER+PR+ tumors. A comparative genomic hybridization array technique was used to examine 25 ER+PR+ and 23 ER+PR- tumors. Tissue microarrays composed of 50 ER+PR+ and 50 ER+PR- tumors were developed to validate the comparative genomic hybridization array results. The genes of interest were analyzed by fluorescence in situ hybridization. The ER+PR- group had a slightly different genomic profile when compared with ER+PR+ tumors. Chromosomes 17 and 20 contained the most overlapping gains, and chromosomes 3, 8, 9, 14, 17, 21, and 22 contained the most overlapping losses when compared with the ER+PR+ group. The gained regions, 17q23.2-q23.3 and 20q13.12, and the lost regions, 3p21.32-p12.3, 9pter-p13.2, 17pter-p12, and 21pter-q21.1, occurred at different alteration frequencies and were statistically significant in the ER+PR- tumors compared with the ER+PR+ tumors. ER+PR- breast tumors have a different genomic profile compared with ER+PR+ tumors. Differentially lost regions in the ER+PR- group included genes with tumor suppressor functions and genes involved in apoptosis, mitosis, angiogenesis, and cell spreading. Differentially gained regions included genes such as MAP3K3, RPS6KB1, and ZNF217. Amplification of these genes could contribute to resistance to apoptosis, increased activation of the PI3K/Akt/mTOR pathway, and the loss of PR in at least some ER+PR- tumors.Cancer Genetics 04/2012; 205(4):138-46.
Article: Cytogenetic characterization of NCI-H69 and NCI-H69AR small cell lung cancer cell lines by spectral karyotyping.[show abstract] [hide abstract]
ABSTRACT: Small cell lung cancer (SCLC) shows an excellent sensitivity to chemotherapy, but commonly develops resistance after a few months. An early identification of a genomic marker in drug discovery may help to select patients who would respond to treatment in clinical trials. Herein, we characterized the parental NCI-H69 (sensitive) and NCI-H69AR (anthracycline-resistant) cell lines by G-banding and spectral karyotyping (SKY). In the H69 cell line, SKY allows us to redefine three alterations that are not well characterized by G-banding and to confirm seven. For H69AR, SKY redefined 10 chromosomal alterations and confirmed four observed by G-banding. Fluorescence in situ hybridization confirmed the amplification of the MYCN gene (dmin or hsr) in these two cell lines, although only the H69AR cell line showed MYCN amplification in the form of homogeneously staining regions. It should be noted that a new derivative chromosome appears in the H69AR cell line, a der(16)t(3;16;18;5;18), characterized by SKY as showing 18q amplification. Amplification of genes located in this region may correlate with resistance to anticancer therapies. We suggest that the 18q marker may have a broader application in SCLC. In conclusion, SKY provides a useful complementary technique to routine cytogenetics for the accurate characterization of SCLC cell lines and could provide some relevant information concerning regions involved in chemoresistance.Cancer genetics and cytogenetics 07/2009; 191(2):97-101. · 1.54 Impact Factor
Article: FISH and immunohistochemical status of the hepatocyte growth factor receptor (c-Met) in 184 invasive breast tumors.Breast cancer research: BCR 05/2009; 11(2):402. · 5.24 Impact Factor