Somatic genetic alterations (loh) in benign, borderline and invasive ovarian tumours: Intratumoral molecular heterogeneity

Zborovskaya, I.А.; Gasparian, Alexander V.; Karseladze, Appolon; Elcheva, Irina; Трофимова, Е. А.; Driouch, Keltouma; Trassard, Martine; Tatosyan, A. G.; Lidereau, Rosette

doi:10.1002/(sici)1097-0215(19990909)82:6<822::aid-ijc9>3.3.co;2-9

Cited by 6 publications

(8 citation statements)

References 10 publications

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“…Some studies of benign ovarian tumors have reported low or zero rates of loss leading to speculation that these represent a distinct biological entity from malignant ovarian tumors 11, 26, 27. However, such conclusions have been based on very small numbers of tumors.…”

Section: Discussionmentioning

confidence: 47%

Cytotoxic/natural killer cell cutaneous lymphomas

Santucci

Pimpinelli

Massi

et al. 2003

Cancer

245

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BACKGROUNDCutaneous lymphomas expressing a cytotoxic or natural killer (NK) cell phenotype represent a group of lymphoproliferative disorders for which there is currently much confusion and little consensus regarding the best nomenclature and classification.METHODSThis study analyzes 48 cases of primary cutaneous lymphoma expressing cytotoxic proteins and/or the NK cell marker, CD56. These cases were collected for a workshop of the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force, to better clarify the clinical, morphologic, and phenotypic features of these uncommon tumors.RESULTSSeveral categories with different clinical and pathologic features were delineated: 1) aggressive, CD8+, epidermotropic, cytotoxic T‐cell lymphoma; 2) mycosis fungoides, cytotoxic immunophenotype variant; 3) subcutaneous panniculitis‐like T‐cell lymphoma; 4) NK/T‐cell lymphoma, nasal type; 5) CD4+, NK cell lymphoma; 6) blastoid NK cell lymphoma; (7) intravascular NK‐like lymphoma; and 8) cytotoxic, peripheral T‐cell lymphoma.CONCLUSIONSOur data show that primary cutaneous cytotoxic/NK cell lymphomas include distinct groups of diseases, clinically, histologically, and biologically. Because the finding of a cytotoxic phenotype often has prognostic significance, the routine use of cytotoxic markers in the diagnosis and classification of cutaneous lymphomas should be expanded. Cancer 2003;97:610–27. © 2003 American Cancer Society.DOI 10.1002/cncr.11107

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Section: Discussionmentioning

confidence: 47%

Cytotoxic/natural killer cell cutaneous lymphomas

Santucci

Pimpinelli

Massi

et al. 2003

Cancer

245

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“…DCC gene belongs to a family of dependence receptors and locates on chromosomal region 18q21, which is one of the most commonly deleted regions in epithelial ovarian cancer detected by loss of heterozygosity 24 and comparative genomic hybridization analyses. 25 In the present study, the existence of a common precursor cell of stroma and epithelium is supported by the notion that loss of the DCC locus, the most frequently observed alteration in this study, was detected either in both epithelial and stromal compartments of the tumor or in none of them.…”

Section: Discussionmentioning

confidence: 99%

Frequent gene dosage alterations in stromal cells of epithelial ovarian carcinomas

Tuhkanen

Anttila

Kosma

et al. 2006

Intl Journal of Cancer

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Stromal cells are an active and integral part of epithelial neoplasms. We have previously observed allelic imbalance on chromosome 3p21 in both stromal and epithelial cells of ovarian tumors. This study was designed to explore gene dosage alterations throughout human chromosomes from stromal and epithelial cells of epithelial ovarian carcinomas. Thirteen stromal and 24 epithelial samples, microdissected from epithelial ovarian carcinomas, were analyzed using multiplex ligation-dependent probe amplification technique. Analysis covered 110 cancer related genes. Frequent genetic alterations were detected both in the stroma and epithelium of ovarian carcinomas. The mean number of altered genes per tumor was 10.8 in stroma and 23.6 in epithelium. In the stroma, the mean number of gains was 6.6 and of losses 4.2 and in the epithelium 13.7 and 9.9. The high number of changes associated with advanced tumor stage (p 5 0.035) and death due to ovarian cancer (p 5 0.032). The most frequent alteration was the deletion of the deleted in colorectal carcinoma (DCC) on chromosome 18q21.3 in 62% of samples. Loss of DCC was related to endometrioid subtype (p 5 0.033). Large chromosomal aberrations were detected on the basis of alterations in adjacent genes. Most importantly, 38 genes showed similar genetic alterations (gain-gain or loss-loss) in stromal and epithelial compartments of 11 tumor pairs. Thus, frequent genetic alterations in stromal cells of epithelial ovarian carcinomas resembled those of malignant epithelial cells and may indicate a common precursor cell type. Epithelial-mesenchymal transition may generate transformed cancer cells and modify the tumor microenvironment with distinct properties. ' 2006 Wiley-Liss, Inc.

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“…29,30 In an allelotype study of ovarian tumors, which included use of one marker at 18q, there was frequent allelic loss at D18S50 (18q23) in high-grade and -stage ovarian carcinomas, but not in well-differentiated carcinomas, borderline or benign tumors. 31 Interestingly, in a recent genome-wide analysis of copy number changes in ovarian carcinoma, an association between loss of 18q and reduced survival duration was found. 32 However, multivariate analysis of our data showed only tumor grade to be an independent prognostic factor, not tumor stage or LOH status.…”

Section: Discussionmentioning

confidence: 99%

Allelic Analysis of Serous Ovarian Carcinoma Reveals Two Putative Tumor Suppressor Loci at 18q22-q23 Distal to SMAD4, SMAD2, and DCC

Lassus

Salovaara

Aaltonen

et al. 2001

The American Journal of Pathology

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The distal half of chromosome arm 18q is frequently lost in ovarian carcinoma. To define the putative tumor suppressor locus/loci more precisely we performed allelic analysis with 27 polymorphic microsatellite markers located at 18q12.3-q23 in 64 serous and 9 mucinous ovarian carcinomas. Fifty-nine percent of the serous carcinomas, but only one (11%) of mucinous carcinomas, showed allelic loss at one or more loci (P ‫؍‬ 0.018). In serous carcinomas, deletions were found to be associated with tumor grade and poor survival. The highest frequency of losses was detected at the distal part, 18q22-q23. Two minimal common regions of loss (MCRL) were identified at this region: MCRL1 between D18S465 and D18S61 at 18q22 (3.9 cM) and MCRL2 between D18S462 and D18S70 at 18q23 (5.8 cM). At 18q21.1, proximal to the MCRLs, there are three candidate tumor suppressor genes: SMAD4 (DPC4), SMAD2, and DCC. Their protein expression was studied by immunohistochemistry in normal ovarian tissue and serous carcinomas. Lost or very weak expression of SMAD4, SMAD2 and DCC was found in 28, 28, and 30% of serous carcinomas, respectively. Comparison of allelic loss and protein expression status indicated that none of these genes alone could be the target for the frequent allelic loss at 18q21.1. Together, these genes may account for a substantial proportion of the events, but not all of them. Thus, we propose that the frequent allelic loss at 18q is because of the effect of multiple genes, and there is at least one as yet unidentified tumor suppressor gene at 18q residing distal to SMAD4, SMAD2, and DCC involved in serous ovarian carcinoma. (Am J Pathol 2001, 159:35-42) On the basis of comparative genomic hybridization analyses, the distal half of 18q is a site of frequent loss of genetic material in ovarian carcinoma. 1,2 Three candidate tumor suppressor genes have been identified at 18q21.1: SMAD4 (DPC4), SMAD2, and DCC, 3-5 but few mutations in these genes have been detected in ovarian carcinoma. 6 -8 Ovarian carcinoma originates from the surface epithelium of the ovary. DCC has been shown to be expressed in the surface epithelium, 9 but it is not known if SMAD4 and SMAD2 are expressed in these cells. Furthermore, it is unknown if the expression of DCC, SMAD4, and SMAD2 is lost during malignant transformation. Previously, allelic loss has been studied with several markers at 18q21 in ovarian carcinoma, but fine allelotyping has not been performed at more distal regions of 18q (18q22-q23), which is the site of most frequent loss as suggested by comparative genomic hybridization results. 1,2 Ovarian carcinoma shows several different histological types, including serous, mucinous, endometrioid, and clear cell carcinomas. There is an increasing amount of biological and molecular evidence that different histological types of ovarian carcinoma should be regarded as distinct entities. 10 -14 The most common form of ovarian carcinoma is the serous histological type, which accounts for ϳ55% of all cases. In our previous comparative genomic hybri...

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Somatic genetic alterations (loh) in benign, borderline and invasive ovarian tumours: Intratumoral molecular heterogeneity

Cited by 6 publications

References 10 publications

Cytotoxic/natural killer cell cutaneous lymphomas

Cytotoxic/natural killer cell cutaneous lymphomas

Frequent gene dosage alterations in stromal cells of epithelial ovarian carcinomas

Allelic Analysis of Serous Ovarian Carcinoma Reveals Two Putative Tumor Suppressor Loci at 18q22-q23 Distal to SMAD4, SMAD2, and DCC

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