Four regions of allelic imbalance on 17q12-qter associated with high-grade breast tumors

Plummer, Sarah J.; Paris, Mark; Myles, Jonathan; Tubbs, Raymond R.; Crowe, Joseph P.; Casey, Graham

doi:10.1002/(sici)1098-2264(199712)20:4<354::aid-gcc6>3.0.co;2-0

Cited by 50 publications

(24 citation statements)

References 42 publications

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“…The localizations of the SROs de®ned in this study are in good concordance with previously reported data ( Figure 5). Indeed, de®nition of SRO 2 and SRO 3 is coherent with that of Plummer et al (1997b). Using slightly di erent sets of markers this group concluded to the existence of two domains of imbalance which they localized in close proximity to ours.…”

Section: De®nition Of Common Regions Of Imbalancementioning

confidence: 62%

“…The number of regions showing allelic imbalance (AI) has increased along with the number and the informativeness of available polymorphic markers. Combining results presented in two recent studies leads to conclude to the existence of at least four regions of allelic imbalance along 17q, one at 17q21, two in the 17q22 ± q24 region and one at 17q25 (Niederacher et al, 1997;Plummer et al, 1997b). However, the nature of the anomalies involving these regions remains uncertain.…”

Section: Introductionmentioning

confidence: 88%

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17q21-q25 aberrations in breast cancer: combined allelotyping and CGH analysis reveals 5 regions of allelic imbalance among which two correspond to DNA amplification

et al. 1999

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Chromosome 17q is frequently rearranged in breast cancer. Allelotyping studies have proposed the existence of at least four regions of allelic imbalance (AI). Here we present a study combining allelotyping using 19 CA repeat markers mapping in the 17q21 ± 25 region and molecular cytogenetics (CGH and FISH). Allelotyping was undertaken on 178 pairs of cognate tumor and normal DNA in order to determine the number of regions of AI and de®ne the shortest overlaps. AI ranged from 34 ± 54% of the informative cases according to the marker and, overall, 66% of the tumors presented AI at one of the markers tested. Analysis of the patterns of imbalances revealed at least ®ve common regions of imbalance respectively de®ned by markers: D17S855, which is intragenic of BRCA1 (SRO 1), D17S1607 (SRO 2), D17S1855 (SRO 3), between D17S789 and D17S785 (SRO 4) and D17S784 (SRO 5). In order to characterize the nature of the genetic events revealed by allelotyping we performed CGH analysis on a subset of 43 tumors presenting variable patterns of imbalance. CGH showed that AI at 17q could represent four di erent types of genetic events: loss of chromosome 17, gain of 17q, gain of 17q22 ± q24, loss of 17q11 ± q21 and/ or 17q25 ± qter. Some of these anomalies could occur concomitantly within the same tumor. Since 35% of the tumors analysed by CGH presented gains, these data indicated that AI at 17q were not solely indicative of losses of genetic material and could also represent DNA ampli®cation. Gains were most commonly observed in the 17q23 ± q24 regions. This suggested that AI in SRO 2 and SRO 3 corresponded to DNA ampli®cation. To assess this, we isolated BAC clones by PCR screening for markers D17S1607 and D17S1855 and used these in FISH experiments on six breast tumor cell lines and 14 breast cancer specimens. FISH results showed that both D17S1607 and D17S1855 were frequently involved in DNA ampli®cation (8 ± 30 copies). Altogether, our data show that allelotyping can be e ciently used in amplicon mapping. Clinico-pathological correlations indicated that imbalance at 17q preferentially occurred in high grade, PR-and ERBB2 ampli®ed tumors.

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Section: De®nition Of Common Regions Of Imbalancementioning

confidence: 62%

Section: Introductionmentioning

confidence: 88%

17q21-q25 aberrations in breast cancer: combined allelotyping and CGH analysis reveals 5 regions of allelic imbalance among which two correspond to DNA amplification

et al. 1999

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“…The arrowhead is placed to indicate the minimal region of imbalance deduced by the LOH analysis of ovarian tumors LOH analysis as a tool for establishing the minimal region of LOH for the future identi®cation of tumor suppressor will continue to be challenging in the absence of a consortium for this purpose. Recent LOH studies have indicated the presence of a tumor suppressor on 17q24-25 in breast cancer (Cornelis et al, 1993;Cropp et al, 1993;Kalikin et al, 1996;Plummer et al, 1997b;Phelan et al, 1998), and in squamous cell carcinomas of the esophagus (von Breven et al, 1998). In the latter study, the highest frequency of LOH was observed in D17S801 in a series of sporadic tumors, and this locus overlaps the 17q24-25 interval which showed a signi®cant linkage to the tylosis-associated cancer susceptibility gene (TOC) (Kelsell et al, 1996).…”

Section: Discussionmentioning

confidence: 96%

Allelotyping defines minimal imbalance at chromosomal region 17q25 in non-serous epithelial ovarian cancers

et al. 2000

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Allelic deletions of multiple chromosome 17q loci in sporadic ovarian cancer of epithelial origin suggest that inactivation of tumor suppressor gene(s) in these regions may be important for ovarian tumorigenesis. To further de®ne the pattern of allelic imbalance in epithelial ovarian tumors of di erent histologies, a PCR-based assay was used to assess loss of heterozygosity (LOH) of polymorphic markers representative of TP53, BRCA1, NME1 and GH1, and region 17q23-25. LOH was observed for at least one marker in 68% of malignant tumors (n=60) and in 18% tumors of borderline malignancy (n=11), but not in benign tumors (n=5). The highest frequency of LOH in malignant tumors (64%) was observed with D17S801 on 17q25. Ten of 39 malignant ovarian tumors displaying LOH of at least one 17q marker, displayed a LOH pattern enabling the determination of a minimal region of overlapping deletion de®ned by D17S795 and D17S801. One borderline tumor also displayed an interstitial LOH pattern that overlapped this 17q25 minimal region of deletion. The histologies of malignant tumors displaying a pattern indicative of interstitial 17q deletions were of the endometrioid, clear cell and mucinous epithelial types. As the minimal region of overlap de®ned by these tumors overlap regions deleted in malignant tumors of all histologic types, and in a tumor of borderline malignancy, the 17q25-tumor suppressor may be implicated in the development of all types of epithelial ovarian tumors.

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“…The gene encoding 17HSD type 1 is located at 17q12 -21, a region that often is rearranged in breast cancer (Plummer et al, 1997, Kauraniemi et al, 2001. In a recent study, we found amplification of the gene encoding 17HSD type 1 in 14.5% of the breast tumours (Gunnarsson et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

17β-Hydroxysteroid dehydrogenases involved in local oestrogen synthesis have prognostic significance in breast cancer

2005

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The 17b-hydroxysteroid dehydrogenase (17HSD) enzymes are involved in the local regulation of sex steroids. The 17HSD type 1 enzyme catalyses the interconversion of the weak oestrone (E1) to the more potent oestradiol (E2), whereas 17HSD type 2 catalyses the oxidation of E2 to E1. The aim of this study was to correlate the expression of these enzymes in the tumour with the recurrence-free survival of tamoxifen-treated breast cancer patients. We used real-time reverse transcriptase PCR to investigate the mRNA expression of 17HSD types 1 and 2 in tumour samples from 230 postmenopausal patients. For the patients with oestrogen receptor (ER)-positive breast cancer, we found a statistically significant positive correlation between recurrence-free survival and expression of 17HSD type 2 (P ¼ 0.026). We examined the ratio of 17HSD types 2 and 1, and ER-positive patients with low ratios showed a significantly higher rate of recurrence than those with higher ratios (P ¼ 0.0047). ER positive patients with high expression levels of 17HSD type 1 had a significantly higher risk for late relapse (P ¼ 0.0051). The expression of 17HSD types 1 and 2 in breast cancer differs from the expression of these enzymes in normal mammary gland, and this study indicates that the expression has prognostic significance in breast cancer.

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Four regions of allelic imbalance on 17q12-qter associated with high-grade breast tumors

Cited by 50 publications

References 42 publications

17q21-q25 aberrations in breast cancer: combined allelotyping and CGH analysis reveals 5 regions of allelic imbalance among which two correspond to DNA amplification

17q21-q25 aberrations in breast cancer: combined allelotyping and CGH analysis reveals 5 regions of allelic imbalance among which two correspond to DNA amplification

Allelotyping defines minimal imbalance at chromosomal region 17q25 in non-serous epithelial ovarian cancers

17β-Hydroxysteroid dehydrogenases involved in local oestrogen synthesis have prognostic significance in breast cancer

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