Loss of heterozygosity from the short arm of chromosome 8 is an early event in breast cancers

Yarernko, M. Lisa; Recant, Wendy; Westbrook, Carol A.

doi:10.1002/gcc.2870130308

Cited by 66 publications

(39 citation statements)

References 17 publications

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“…The ability to detect a clinical utility of 8p deletion measurement in small cohorts is obviously caused by the high rate of positive cases (almost 50%) and a particularly strong prognostic impact of this feature. It is noteworthy, however, that several other small cohorts failed to find associations with tumor phenotype 14,16,[34][35][36]59 or patient death. [34][35][36] Limitations of our study include that retrospectively collected data are used for estimating the prognostic value of 8p deletion.…”

Section: Discussionmentioning

confidence: 95%

8p deletion is strongly linked to poor prognosis in breast cancer

Lebok

Mittenzwei

Kluth

et al. 2015

Cancer Biology & Therapy

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Deletions of chromosome 8p occur frequently in breast cancers, but analyses of its clinical relevance have been limited to small patient cohorts and provided controversial results. A tissue microarray with 2,197 breast cancers was thus analyzed by fluorescence in-situ hybridization using an 8p21 probe in combination with a centromere 8 reference probe. 8p deletions were found in 50% of carcinomas with no special type, 67% of papillary, 28% of tubular, 37% of lobular cancers and 56% of cancers with medullary features. Deletions were always heterozygous. 8p deletion was significantly linked to advanced tumor stage (P < 0.0001), high-grade (P < 0.0001), high tumor cell proliferation (Ki67 Labeling Index; P < 0.0001), and shortened overall survival (P < 0.0001). For example, 8p deletion was seen in 32% of 290 grade 1, 43% of 438 grade 2, and 65% of 427 grade 3 cancers. In addition, 8p deletions were strongly linked to amplification of MYC (P < 0.0001), HER2 (P < 0.0001), and CCND1 (p D 0.001), but inversely associated with ER receptor expression (p D 0.0001). Remarkably, 46.5% of 8p-deleted cancers harbored amplification of at least one of the analyzed genes as compared to 27.5% amplifications in 8p-non-deleted cancers (P < 0.0001). In conclusion, 8p deletion characterizes a subset of particularly aggressive breast cancers. As 8p deletions are easy to analyze, this feature appears to be highly suited for future DNA based prognostic breast cancer panels. The strong link of 8p deletion with various gene amplifications raises the possibility of a role for regulating genomic stability.

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Section: Discussionmentioning

confidence: 95%

8p deletion is strongly linked to poor prognosis in breast cancer

Lebok

Mittenzwei

Kluth

et al. 2015

Cancer Biology & Therapy

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“…The DLC-1 gene was found to be located at 8p21.3-22 (Yuan et al, 1998), a region frequently deleted in various cancer cells including hepatocellular, lung, colorectal, prostate, and breast cancer (Emi et al, 1992;Fujiwara et al, 1994;Yaremko et al, 1995;Wistuba et al, 1999), and has been reported to be deleted in HCC cell lines and in primary tumors (Yuan et al, 1998;Ng et al, 2000). However, the mechanism of the loss of DLC-1 expression without genomic deletion has not been explored.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional silencing of the DLC-1 tumor suppressor gene by epigenetic mechanism in gastric cancer cells

et al. 2003

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Southern analysis showed that seven of nine human gastric cancer cell lines did not express DLC-1 mRNA, but contained the DLC-1 gene. To identify the mechanism of the loss of DLC-1 mRNA expression in these cell lines, we investigated the methylation status of DLC-1 gene by using methylation-specific PCR (MSP) and Southern blot, and found that five of seven DLC-1 nonexpressing gastric cancer cell lines were methylated in the DLC-1 CpG island. Treatment with 5-aza-2 0 -deoxycytidine (5-Aza-dC) induced DLC-1 mRNA expression in the gastric cancer cell lines that have the methylated alleles. Studies using SNU-601 cell line with methylated DLC-1 alleles revealed that nearly all CpG sites within DLC-1 CpG island were methylated, and that the in vitro methylation of the DLC-1 promoter region is enough to repress DLC-1 mRNA expression, regardless of the presence of transcription factors capable of inducing this gene. In all, 29 of 97 (30%) primary gastric cancers were also shown to be methylated, demonstrating that methylation of the DLC-1 CpG island is not uncommon in gastric cancer. In addition, we demonstrated that DLC-1 mRNA expression was induced, and an increase in the level of acetylated H3 and H4 was detected by the treatment with trichostatin A (TSA) in two DLC-1 nonexpressing cell lines that have the unmethylated alleles. Taken together, the results of our study suggest that the transcriptional silencing of DLC-1, by epigenetic mechanism, may be involved in gastric carcinogenesis.

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“…Regions of 8p22-23 have been implicated by LOH analysis as harbouring suppressor genes relevant to the progression of many other tumour types (Suzuki et al, 1995;Yaremko et al, 1995;Bova et al, 1996). Whether these are all independent targets, or whether there are common targets inactivated in a wide variety of tumours will not be known until the relevant genes have been cloned.…”

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confidence: 99%