Identification of a 1300 kilobase deletion unit on chromosome 7q31.3 in invasive epithelial ovarian carcinomas

Edelson, Mitchell I.; Scherer, Stephen W.; Tsui, Lap‐Chee; Welch, William R.; Bell, Deborah F.; Rs, Berkowitz; Mok, Samuel C.

doi:10.1038/sj.onc.1201271

Cited by 46 publications

(34 citation statements)

References 20 publications

(23 reference statements)

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“…One is in the vicinity of D7S658 at 7q22.2 and another distal to D7S522 at 7q31. This is in agreement with several other studies of ovarian carcinomas (Kerr et al, 1996;Koike et al, 1997;Edelson et al, 1997). A candidate TSG on 7q (Lane et al, 1996;Li et al, 1996) is the gene for plasminogen activator inhibitor (PAI-1) which has been reported to show a rearrangement in an Abbreviations: Het, retention of constitutional heterozygosity; loh, loss of constitutional heterozygosity; blank space, not informative due to constitutional homozygosity or not done.…”

Section: Discussionsupporting

confidence: 81%

Loss of heterozygosity on chromosomes 7p, 7q, 9p and 11q is an early event in ovarian tumorigenesis

et al. 1998

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Section: Discussionsupporting

confidence: 81%

Loss of heterozygosity on chromosomes 7p, 7q, 9p and 11q is an early event in ovarian tumorigenesis

et al. 1998

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“…Although deletions of chromosome 7q31 is reported in various kinds of carcinomas including serous OC, 22 LOH of this locus was closely associated with only mucinous LMP in this study. High frequency of LOH at 7q35 where caspase-2 and Fas-activated serine/threonine kinase are assigned 23,24 has not been reported in any tumors previously.…”

Section: Loh Analysis In Ovarian Tissues From Different Lesionscontrasting

confidence: 55%

Comprehensive allelotype study of ovarian tumors of low malignant potential: Potential differences in pathways between tumors with and without genetic predisposition to invasive carcinoma

Nakayama

Takebayashi

Namiki³

et al. 2001

Int. J. Cancer

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Ovarian tumors of low malignant potential (LMP) are intermediate between adenomas and ovarian carcinomas (OC); however, the relevance of LMP to ovarian carcinogenesis is not clear. We performed a comparative analysis of allelotypes in 50 cases of LMP (42 mucinous and 8 serous) and 23 cases of OC (15 mucinous and 8 serous) to investigate any differences in genetic changes. Analysis of loss of heterozygosity (LOH) using 25 microsatellite markers reportedly associated with OC revealed that the total LOH frequency at each marker was significantly lower in LMP than in OC (p < 0.01). However, 9 (36%) loci showed higher LOH frequency in mucinous LMP than in mucinous OC. A genome-wide scan for LOH using 91 microsatellite markers and fine mapping revealed that LOH at D7S1805 (7q35) is characteristic of mucinous LMP (19.4% in mucinous LMP, 8.3% in mucinous OC). We further studied LOH in 3 cases of mucinous OC that were accompanied by mucinous LMP lesions. In 2 cases, LOH frequency was higher in the carcinoma portion than in the morphologically LMP portion. The other case showed microsatellite instability in the morphologically LMP portion and LOH in the carcinoma portion. Our results suggest the presence of an LMP-to-OC developmental sequence and the existence of a subset of LMP that does not develop into OC in the mucinous subtype of ovarian tumors. © 2001 Wiley-Liss, Inc. Key words: ovarian carcinogenesis; genome; mucinous LMP; serous LMP; loss of heterozygosity (LOH)Among gynecologic malignancies, ovarian carcinoma (OC) is the leading cause of death. 1,2 Ovarian tumors of low malignant potential (LMP) are a distinctive subtype of ovarian epithelial tumor characterized as an intermediate stage between clearly benign and OC. One of the histologic criteria of LMP or borderline malignancy is atypical epithelial proliferation without ovarian stromal invasion. It remains to be determined whether LMP is a precursor of OC or a unique type of tumor that will not progress to OC.It is well established that carcinogenesis of solid tumors requires a series of genetic changes involving activation of oncogenes and inactivation of tumor suppressor genes. In OC, mutational activation of the K-ras gene, inactivation of the p53 gene and overexpression/amplification of the erb-B2 gene have been reported. [3][4][5] Mutations and loss of heterozygosity (LOH) of the p53 tumor suppressor gene on chromosome 17p13.1 are rare events in LMP. 6 LOH of chromosomes 7p, 7q, 9q and 11q has been reported to be involved in the early stages of ovarian carcinogenesis. 7 The incidence of K-ras mutations is higher in OC than in LMP, especially in the mucinous subtype. 8 These findings suggest that LMP may represent a pathologic continuum between benign tumors and OC. However, the molecular genetic changes in LMP are not well understood compared with OC, as only a few instances have been analyzed of LOH occurring in a small number of cases of LMP. 8 -11 To elucidate the biological relevance of LMP to ovarian carcinogenesis, we compared allelotypes between...

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“…Eight of these markers map to the region between 7q31.1 and 7q31.2, a region which has been shown to exhibit a high frequency of allele loss in several tumor types (Achille et al, 1996;Devilee et al, 1997;Edelson et al, 1996;Koike et al, 1997;Lin et al, 1996;Oakahashi et al, 1995;Zenklusen et al, 1994aZenklusen et al, , b, 1995a. Also shown in Table 1 are the overall results showing the number of informative cases, the number of cases with LOH, and %LOH for the entire set of 42 tumors (FTC, PTC, and FA).…”

Section: Resultsmentioning

confidence: 99%

“…Several reports have shown that LOH at 7q31 is a frequent event in the development of breast, ovarian, and prostate cancer (Devilee et al, 1997;Edelson et al, 1996;Koike et al, 1997;Lin et al, 1996;Oakahashi et al, 1995;Zenklusen et al, 1994aZenklusen et al, ,b, 1995a. We recently demonstrated that the same region shows frequent loss in sporadic renal cell carcinomas (Shridhar et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…Loss of heterozygosity (LOH) in a chromosomal region is generally the ®rst indication that a speci®c region may harbor a putative tumor suppressor gene (TSG) (Edelson et al, 1996;Knudson, 1993;Lin et al, 1996;Weinberg, 1991;Zenklusen et al, 1994a). Recent studies have shown frequent LOH of microsatellite markers on the long arm of chromosome 7, speci®cally at band q31 in several types of tumor including breast (Devilee et al, 1997;Lin et al, 1996;Zenklusen et al, 1994a), ovarian (Koike et al, 1997;Zenklusen et al, 1995a), pancreatic (Achille et al, 1996), prostatic (Oakahashi et al, 1995;Zenklusen et al, 1994b), and squamous cell carcinoma of the head and neck (Zenklusen et al, 1995b).…”

Section: Introductionmentioning

confidence: 99%

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Differential loss of heterozygosity at 7q31.2 in follicular and papillary thyroid tumors

et al. 1998

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We analysed 42 di erentiated thyroid tumors including 15 follicular adenomas (FA), 13 papillary thyroid cancers (PTC) and 14 follicular thyroid carcinomas (FTC) with 13 microsatellite markers speci®c for the long arm of human chromosome 7 within 7q31; this region is deleted frequently in several other tumor types. Overall, 20 of the 42 samples analysed (48%) displayed LOH with one or more of the markers tested. LOH was detected most frequently (78%) in FTC, the most malignant of the thyroid tumors. A smallest common deleted region (SCDR) was de®ned in this tumor typē anked by markers D7S480 and D7S490. This SCDR is distinct from D7S522, the most commonly deleted locus in many other tumors, which was deleted in only one FTC. D7S522 did show LOH in two of six informative PTCs. None of the PTC and only two of the FAs showed LOH in the FTC SCDR. Since FA is considered a premalignant stage of FTC, our results suggest that inactivation of a putative tumor suppressor at 7q31.2 may be acquired during adenoma to carcinoma progression. The absence of LOH at this locus amongst PTC suggests that inactivation of this tumor suppressor is speci®c for FTC. In conclusion, LOH at 7q31 is a frequent event in di erentiated thyroid cancer, and we have de®ned a 2 cM SCDR speci®c for FTC.

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Identification of a 1300 kilobase deletion unit on chromosome 7q31.3 in invasive epithelial ovarian carcinomas

Cited by 46 publications

References 20 publications

Loss of heterozygosity on chromosomes 7p, 7q, 9p and 11q is an early event in ovarian tumorigenesis

Loss of heterozygosity on chromosomes 7p, 7q, 9p and 11q is an early event in ovarian tumorigenesis

Comprehensive allelotype study of ovarian tumors of low malignant potential: Potential differences in pathways between tumors with and without genetic predisposition to invasive carcinoma

Differential loss of heterozygosity at 7q31.2 in follicular and papillary thyroid tumors

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