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Loss of heterozygosity at 6Q in malignant salivary gland tumors
168
Abstracts
LOSS OF HETEROZYGOSITYAT 6Q IN MALIGNANT SALIVARY GLAND TUMORS
CYTOGENETIC FINDINGS IN 34 PRIMARY NSCLCS
L. Queimado, L. Parreira, A. Reis, C. Martins, J. Rosa Santos, I. Fonseca, J, saares
E. D'Alessandro, F. Brisdelli, ML. Lo Re, C. Ugas, R. Crisci, G. Torresini, GF. Coloni
Centro de InvestigaqOo de Patobiologia Molecular, Instituto Portugu~s de Oncologta Francisco Gentil, Centro Regional de Llsboa
Cattedra di Genetica Medica, Cattedra di Chirurgla Toracica, UniversitO degli Studi de L'Aquila
Terminal deletions of the long arm of chromosome 6 (6q) are the most consistent cytogenetic abnormalities in salivary gland carcinomas and the only cytogenetic event common to all histological subtypes, with the exception of carcinoma ex-pleomorphic adenoma. In an attempt to characterize at the molecular level the frequency and the extension of 6q deletions in salivary gland carcinomas, we have investigated the loss of heterozygosity (LOH) at 6q in a series of 12 tumors, using polymorphic DNA markers. Frozen tumor samples and the normal tissue from each patient were studied by Southern blotting and dinucleotide repeats analysis, using 12 polymorphic markers (1 at 6p, 1 eentromeric, and 10 at 6q). Detailed clinical and histopathological data from all patients and tumors were available. Eleven of twelve cases were informative for at least one locus at 6q. LOH was observed in 4 of the 11 informative cases, all of which were of different histological subtypes. The highest frequency of LOH was found at loci D6S305 at 6q25.2 (2/4 cases) and D6S37 (2/6 cases) at 6q26-27. The patterns observed were compatible with terminal deletions in 3 cases and with an interstitial deletion in the remaining case. Furthermore, the data suggests that the smallest region of overlapped deletion occurs between 6q25.2 and 6(t27. In summary, LOH at 6q was found in 37% of the cases in this series of salivary gland carcinomas. Although preliminary, our results support the assumption that loss of genetic material at 6q is a frequent and probably an important event in salivary gland carcinogenesis. The analysis of a larger series of eases and the use of more polymorphic markers will likely clarify the real incidence of 6q deletions and the smallest regions of overlapped deletions in these neoplasms.
Cytogenetic studies on Non-Small Cell Lung Cancer (NSCLC) are limited and until now it has not been possible to identify any specific chromosomal marker of this neoplasia (1, 2, 3). This cytogenetic analysis was performed on 34 primary NSCLCs (9 ADC, 25 SQC) essentially by direct method and short term cultures. Clonal structural and numerical aberrations were found in 16 cases. Identification of clonal rearrangements was possible in 9 specimens, 6 SQC and 3 ADC. Both histological types mostly showed a complex cytogenetic pattern. Neartriploidy was observed in > 80% of tumors with clonal aberrations. Chromosomes 8, 16, 17, 18 and Y were frequently lost. Moreover, l p, l q, 2p, 3p, 3q, 6(t, 7p, 7q, 9p, 1 lq, 13q, l,J,q, 15q, 19q were preferentially involved in rearrangements with breakpoints clustered essentially in pericentromeric regions. These structural changes have lead to losses oftq, 7q, 9p, 10p, 13q, 14q and gain of7p, 9q. The most frequent structural aberrations were i(gq), t(9; 15), i(7p), t(l 3;19), del(3p) and del(tq). A different distribution of chromosome rearrangements and aneuploidies was observed in ADC and SQC, but recurrent cytogenetic aberrations found did not show any association with clinical parameters. References 1. Testa J.R. et al (1994) Cytogenetic analysis of 63 non-small cell lung carcinomas: recurrent chromosome alterations amid frequent and widespread genomic upheaval. Genes Chromosom Cancer 11:178-194. 2. Lukeis R. et al. (I 990) Cytogenetics of non-small lung cancer, analysis of consistent non-random abnormaities. Genes Chromosom Cancer 2:116124. 3. D'Alessandro E. et al (1994) Cytogenetic findings in primary Non-Small Cell Lung Cancer. Tumori 80: 151-156.
Acknowledgements L.Q. was supported by the Junta Nacional de Investiga~o Cientifica e Tecnol6gica (JNICT). Probes p308 and phMnSOD4 were kindly provided by Prof. E. W. Jabs, and. G. I. Bell, respectively.
Abstracts
LOSS OF HETEROZYGOSITYAT 6Q IN MALIGNANT SALIVARY GLAND TUMORS
CYTOGENETIC FINDINGS IN 34 PRIMARY NSCLCS
L. Queimado, L. Parreira, A. Reis, C. Martins, J. Rosa Santos, I. Fonseca, J, saares
E. D'Alessandro, F. Brisdelli, ML. Lo Re, C. Ugas, R. Crisci, G. Torresini, GF. Coloni
Centro de InvestigaqOo de Patobiologia Molecular, Instituto Portugu~s de Oncologta Francisco Gentil, Centro Regional de Llsboa
Cattedra di Genetica Medica, Cattedra di Chirurgla Toracica, UniversitO degli Studi de L'Aquila
Terminal deletions of the long arm of chromosome 6 (6q) are the most consistent cytogenetic abnormalities in salivary gland carcinomas and the only cytogenetic event common to all histological subtypes, with the exception of carcinoma ex-pleomorphic adenoma. In an attempt to characterize at the molecular level the frequency and the extension of 6q deletions in salivary gland carcinomas, we have investigated the loss of heterozygosity (LOH) at 6q in a series of 12 tumors, using polymorphic DNA markers. Frozen tumor samples and the normal tissue from each patient were studied by Southern blotting and dinucleotide repeats analysis, using 12 polymorphic markers (1 at 6p, 1 eentromeric, and 10 at 6q). Detailed clinical and histopathological data from all patients and tumors were available. Eleven of twelve cases were informative for at least one locus at 6q. LOH was observed in 4 of the 11 informative cases, all of which were of different histological subtypes. The highest frequency of LOH was found at loci D6S305 at 6q25.2 (2/4 cases) and D6S37 (2/6 cases) at 6q26-27. The patterns observed were compatible with terminal deletions in 3 cases and with an interstitial deletion in the remaining case. Furthermore, the data suggests that the smallest region of overlapped deletion occurs between 6q25.2 and 6(t27. In summary, LOH at 6q was found in 37% of the cases in this series of salivary gland carcinomas. Although preliminary, our results support the assumption that loss of genetic material at 6q is a frequent and probably an important event in salivary gland carcinogenesis. The analysis of a larger series of eases and the use of more polymorphic markers will likely clarify the real incidence of 6q deletions and the smallest regions of overlapped deletions in these neoplasms.
Cytogenetic studies on Non-Small Cell Lung Cancer (NSCLC) are limited and until now it has not been possible to identify any specific chromosomal marker of this neoplasia (1, 2, 3). This cytogenetic analysis was performed on 34 primary NSCLCs (9 ADC, 25 SQC) essentially by direct method and short term cultures. Clonal structural and numerical aberrations were found in 16 cases. Identification of clonal rearrangements was possible in 9 specimens, 6 SQC and 3 ADC. Both histological types mostly showed a complex cytogenetic pattern. Neartriploidy was observed in > 80% of tumors with clonal aberrations. Chromosomes 8, 16, 17, 18 and Y were frequently lost. Moreover, l p, l q, 2p, 3p, 3q, 6(t, 7p, 7q, 9p, 1 lq, 13q, l,J,q, 15q, 19q were preferentially involved in rearrangements with breakpoints clustered essentially in pericentromeric regions. These structural changes have lead to losses oftq, 7q, 9p, 10p, 13q, 14q and gain of7p, 9q. The most frequent structural aberrations were i(gq), t(9; 15), i(7p), t(l 3;19), del(3p) and del(tq). A different distribution of chromosome rearrangements and aneuploidies was observed in ADC and SQC, but recurrent cytogenetic aberrations found did not show any association with clinical parameters. References 1. Testa J.R. et al (1994) Cytogenetic analysis of 63 non-small cell lung carcinomas: recurrent chromosome alterations amid frequent and widespread genomic upheaval. Genes Chromosom Cancer 11:178-194. 2. Lukeis R. et al. (I 990) Cytogenetics of non-small lung cancer, analysis of consistent non-random abnormaities. Genes Chromosom Cancer 2:116124. 3. D'Alessandro E. et al (1994) Cytogenetic findings in primary Non-Small Cell Lung Cancer. Tumori 80: 151-156.
Acknowledgements L.Q. was supported by the Junta Nacional de Investiga~o Cientifica e Tecnol6gica (JNICT). Probes p308 and phMnSOD4 were kindly provided by Prof. E. W. Jabs, and. G. I. Bell, respectively.