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• W2735403764 abstract "1886 Functional inactivation of tumor-suppressor gene(s) is an essential step in carcinogenesis and progression. Tumor-suppressor genes are generally inactivated by an intragenic point mutation in one allele and the subsequent loss of the corresponding (wild-type) allele, resulting in a condition known as “loss of heterozygosity”(LOH). Somatic alterations in microsatellite sequence due to a deletion or an insertion of one or more repeat units have been termed “microsatellite instabilities” (MSI). MSI is associated with defects in the DNA mismatch-repair machinery, and MSI has been detected in both hereditary and sporadic human cancer. MSI could lead to inactivation of other tumor-suppressor genes. In our previous study, using comparative genomic hybridization (CGH), it was found that primary breast cancer with metastasis (axillary node and/or distant metastasis) acquired deletion on chromosome 22q13 at higher frequency than primary breast cancer without metastasis (unpublished data), suggesting that this region might contain a tumor suppressor gene involved in the metastasis of breast cancer. The objective of this study was to identify the candidate tumor-suppressor gene loci on chromosome 22q13 by PCR-based microsatellite analysis. Sixty-two pairs of matched normal DNA and primary tumor DNA from patients of invasive breast cancer were analyzed by PCR, using 6 fluorescence-labeled primers for polymorphic microsatellite markers spanning chromosome 22q13 (D22S284, D22S276, D22S282, D22S1171, D22S1159, D22S274). The PCR products were electrophoresed on an ABI 310 genetic analyzer; Genescan 2.1 and Genotyper V.2.0 software were used for scanning and analysis of LOH and MSI. Statistical significant association was tested between the occurrence of genetic alterations in microsatellites and clinicopathological data of primary breast cancer in patients with or without metastasis. After excluding the non-informative results, the frequency of allelic alterations among breast cancer with metastasis (35 patients) at marker D22S284, D22S276, D22S282, D22S1171, D22S1159, D22S274, were 13/26(50%), 8/17(47%), 12/30(40%), 14/31(45.2%), 13/24(54.2%), 14/29(48.3%), respectively. In contrast, the corresponding frequency among breast cancer without metastasis (27 patients) were 3/19(15.8%), 8/12(66.7%), 5/23(21.8%), 6/23(26.1%), 13/20(65.0%), 6/19(31.6%), respectively. Comparison of these results with clinicopathological data revealed that allelic alteration at D22S284 significantly associated with breast cancer with metastasis (50% VS15.8%, p=0.04), while allelic alteration at other loci did not reach statistical significance. This data provides evidence suggesting that there may be a candidate tumor suppressor gene near D22S284 loci associated with the metastasis potential of sporadic human breast cancer." @default.
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• W2735403764 date "2005-05-01" @default.
• W2735403764 modified "2023-09-27" @default.
• W2735403764 title "Candidate tumor-suppressor gene loci on chromosome 22q13, D22S284 marker, associated with the metastasis potential of human breast cancer" @default.
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