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Cytogenetic and molecular abnormalities of 6q26-27 region characterize benign surface epithelial ovarian tumors
Abstracts
13 3
CYTOGENETIC AND MOLECULAR ABNORMALITIES OF 6q26-27 REGION CHARACTERIZE BENIGN SURFACE EPITHELIAL OVARIAN TUMORS
THE p21 wArlGENE IS INFREQUENTLYMUTATED IN HUMAN OVARIAN TUMOURS AND p21 wan PROTEIN LEVELSAPPEAR TO BE REGULATED INDEPENDENTLYOF p53 STATUS
MG. TibilettP, B. BernasconiL D. FurlaW, C. Riva ~, M. Trubla 2, F. ZanabonP, PF. Bolls3, C. Capella ~, R. TaramellP
BJ. Milner. ID. Miller*, I. Brown, HC. Kitchener t, D. Parkint, NE. Haites
1-Dipartimento Scienze Cliniche e Biologiche,Universit~ di Pavia in Varese 2-Ospedale S.Raffaele Hospital, MUano 3-CUnica Ostetrica e Ginecologica,UniversitO di Pavia in Varese 4-Dipartimento di Biologia Animale, UniversitO di Catania
The chromosome 6(t deletion is a frequent cytogenetic finding in ovarian carcinoma (Mitelman, 1994),in addition, recent molecular studies have demonstrated LOH on 6q in ovarian malignant serous neoplasms (Foulkes et al 1993). However involvement of chromosome 6 in benign tumors have not been reported so far, and the only karyotypic alteration registered in fibromas, thecomas and adenomas of the ovary is trisomy 12. In recent studies Orphanos et al.(! 995) employing LOH assay in matched tumor/blood material from the same patient, identified three regions on 6(t involved in different histological types of ovarian tumon;, including benign ones. In particular the 6q21-q22.3 region was the most frequently involved (4 out of 7 benign tumors), whereas the 6q26-27 region was altered in only one benign tumor. We cytogenetically investigated seven benign ovarian tumors histologically classified as serous cystoadenomas (2 cases), serous cystoadenofibromas (4 cases) and mucinous cystoadenoma (1 case), according to the criteria of the WHO. Cytogenetic analysis was performed on direct preparation using QFQ handing technique. Dual color FISH was applied to metaphases employing as probes, library of chromosome 6 and YAC clones which map to 6q26-q27 region. Normal karyotypes were found in two cases (2 serous cystoadenofibromas). Clonal chromosome aberrations were detected in 5 diploid tumors, four of which showed 6q deletion. FISH analysis using YACs confirmed molecular deletion of the 6q26-27 region in two cystoadenofibromas and revealed paracentric inversion of the same region in two cases (l mucinous cystoadenoma and l serous cystoadenofibroma). Using conventional cytogenetic and FISH analysis, abnormalities at 6q2627 region were identified in all benign tumors of our series. These findings suggest that: -clonal chromosome anomalies are present in benign ovarian tumors -6q deletion is the most frequent chromosome anomaly involved -molecular alterations of 6q26-27 region are common in our series of serous and mucinous benign ovarian tumors. References Mitelman E 1994 Catalog of chra~mosome abem~tions in cancer V edition Foulkes et al. Br J Cancer 1993; 67:551-559; Orphanos et al Br J Cancer 1995; 71:666-669.
Dept. of Medicine and Therapeutics (Medical Genetics), *Dept. of Pathology and tDept, of Obstetrics and Gynaecology, Aberdeen University Medical School
A panel of 60 ovarian tumours (30 malignant, 15 borderline and 15 benign) have been previously analysed forp53 mutation and protein overexpressionI. Fifteen of the malignants were found to have a p53 mutation and a further three mutants were identified as having abnormally high levels of p53 protein. The same 60 tumours have now been screened for mutation of the p21 war1 gene by loss of heterozygosity and SSCP analysis, and for in situ protein expression levels using immunocytochemistry. No p21 wArlmutations were found, but varying levels and patterns of p21 w^F~expression were detected in 18/30 of the malignants, 7/15 borderlines and 2/15 benigns, p21 w^rl expression could not be correlated with p53 expression. We conclude that, in ovarian cancer, p2 lWAnexpression is regulated independently of p53 status. References 1. Milner, B.J., et al. CANCER RES 1993; 53:2128-2132.
13 3
CYTOGENETIC AND MOLECULAR ABNORMALITIES OF 6q26-27 REGION CHARACTERIZE BENIGN SURFACE EPITHELIAL OVARIAN TUMORS
THE p21 wArlGENE IS INFREQUENTLYMUTATED IN HUMAN OVARIAN TUMOURS AND p21 wan PROTEIN LEVELSAPPEAR TO BE REGULATED INDEPENDENTLYOF p53 STATUS
MG. TibilettP, B. BernasconiL D. FurlaW, C. Riva ~, M. Trubla 2, F. ZanabonP, PF. Bolls3, C. Capella ~, R. TaramellP
BJ. Milner. ID. Miller*, I. Brown, HC. Kitchener t, D. Parkint, NE. Haites
1-Dipartimento Scienze Cliniche e Biologiche,Universit~ di Pavia in Varese 2-Ospedale S.Raffaele Hospital, MUano 3-CUnica Ostetrica e Ginecologica,UniversitO di Pavia in Varese 4-Dipartimento di Biologia Animale, UniversitO di Catania
The chromosome 6(t deletion is a frequent cytogenetic finding in ovarian carcinoma (Mitelman, 1994),in addition, recent molecular studies have demonstrated LOH on 6q in ovarian malignant serous neoplasms (Foulkes et al 1993). However involvement of chromosome 6 in benign tumors have not been reported so far, and the only karyotypic alteration registered in fibromas, thecomas and adenomas of the ovary is trisomy 12. In recent studies Orphanos et al.(! 995) employing LOH assay in matched tumor/blood material from the same patient, identified three regions on 6(t involved in different histological types of ovarian tumon;, including benign ones. In particular the 6q21-q22.3 region was the most frequently involved (4 out of 7 benign tumors), whereas the 6q26-27 region was altered in only one benign tumor. We cytogenetically investigated seven benign ovarian tumors histologically classified as serous cystoadenomas (2 cases), serous cystoadenofibromas (4 cases) and mucinous cystoadenoma (1 case), according to the criteria of the WHO. Cytogenetic analysis was performed on direct preparation using QFQ handing technique. Dual color FISH was applied to metaphases employing as probes, library of chromosome 6 and YAC clones which map to 6q26-q27 region. Normal karyotypes were found in two cases (2 serous cystoadenofibromas). Clonal chromosome aberrations were detected in 5 diploid tumors, four of which showed 6q deletion. FISH analysis using YACs confirmed molecular deletion of the 6q26-27 region in two cystoadenofibromas and revealed paracentric inversion of the same region in two cases (l mucinous cystoadenoma and l serous cystoadenofibroma). Using conventional cytogenetic and FISH analysis, abnormalities at 6q2627 region were identified in all benign tumors of our series. These findings suggest that: -clonal chromosome anomalies are present in benign ovarian tumors -6q deletion is the most frequent chromosome anomaly involved -molecular alterations of 6q26-27 region are common in our series of serous and mucinous benign ovarian tumors. References Mitelman E 1994 Catalog of chra~mosome abem~tions in cancer V edition Foulkes et al. Br J Cancer 1993; 67:551-559; Orphanos et al Br J Cancer 1995; 71:666-669.
Dept. of Medicine and Therapeutics (Medical Genetics), *Dept. of Pathology and tDept, of Obstetrics and Gynaecology, Aberdeen University Medical School
A panel of 60 ovarian tumours (30 malignant, 15 borderline and 15 benign) have been previously analysed forp53 mutation and protein overexpressionI. Fifteen of the malignants were found to have a p53 mutation and a further three mutants were identified as having abnormally high levels of p53 protein. The same 60 tumours have now been screened for mutation of the p21 war1 gene by loss of heterozygosity and SSCP analysis, and for in situ protein expression levels using immunocytochemistry. No p21 wArlmutations were found, but varying levels and patterns of p21 w^F~expression were detected in 18/30 of the malignants, 7/15 borderlines and 2/15 benigns, p21 w^rl expression could not be correlated with p53 expression. We conclude that, in ovarian cancer, p2 lWAnexpression is regulated independently of p53 status. References 1. Milner, B.J., et al. CANCER RES 1993; 53:2128-2132.