Biomedical subjects

O Monni

Publications and source records attributed to O Monni.

25 records · Page 2Linked to original sources

PubMed1998

Presence of high-level DNA copy number gains in gastric carcinoma and severely dysplastic adenomas but not in moderately dysplastic adenomas.

Our aim was to investigate the presence of DNA copy number changes in gastric adenomas and to identify the changes that may play a role in gastric carcinogenesis. DNA copy number changes in 16 patients with gastric adenoma and in 22 tumors from patients with intestinal type gastric carcinomas were studied by using comparative genomic hybridization. DNA copy number changes were found in 44% of the adenoma cases and in 86% of the intestinal type gastric carcinomas. On average, gains were more common than losses (0.9 vs. 0.5 in adenomas and 4.1 vs. 1.8 in carcinomas). In adenomas, the most common gains involved chromosome 8 in 3 cases, and gain of chromosome 7 and 20q was detected in 2 cases. The most frequent losses were observed at 5q (three times). Only adenomas with severe dysplasia showed high-level amplifications that were detected at chromosome 13, 17cen-q22, and 20q12-ter. In gastric cancer, the most common gains were detected at 20q (55%), 17q12-q21 (41%), and 8q (41%), and the most common losses were detected at 18q (41%) and 4q (32%). High-level amplifications were observed at 20q (3 tumors), 17cen-q21 (3 tumors), 2p (1 tumor), and 18q (1 tumor). These findings suggest that the progression of dysplasia is associated with higher levels of DNA copy number increase (e.g., the gains at 17q and 20q), which were typically observed in the intestinal type gastric cancer. Furthermore, the results support the hypothesis that adenoma precedes cancer.

Adenocarcinoma↗

PubMed1998

DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies.

This review summarizes reports of recurrent DNA sequence copy number amplifications in human neoplasms detected by comparative genomic hybridization. Some of the chromosomal areas with recurrent DNA copy number amplifications (amplicons) of 1p22-p31, 1p32-p36, 1q, 2p13-p16, 2p23-p25, 2q31-q33, 3q, 5p, 6p12-pter, 7p12-p13, 7q11.2, 7q21-q22, 8p11-p12, 8q, 11q13-q14, 12p, 12q13-q21, 13q14, 13q22-qter, 14q13-q21, 15q24-qter, 17p11.2-p12, 17q12-q21, 17q22-qter, 18q, 19p13.2-pter, 19cen-q13.3, 20p11.2-p12, 20q, Xp11.2-p21, and Xp11-q13 and genes therein are presented in more detail. The paper with more than 150 references and two tables can be accessed from our web site http://www.helsinki.fi/lglvwww/CMG.html. The data will be updated biannually until the year 2001.

Chromosome Aberrations↗

PubMed1997

BCL2 overexpression associated with chromosomal amplification in diffuse large B-cell lymphoma.

Gene activation by translocation between an oncogene and an immunoglobulin heavy-chain gene, which leads to increased expression of the oncoprotein, is a well-known mechanism in the genesis of B-cell lymphomas. In contrast, the role of gene amplification in activation of oncogenes in non-Hodgkin's lymphomas is poorly characterized. To study the BCL2 amplification we performed comparative genomic hybridization (CGH), Southern blot hybridization, Western analysis, immunohistochemistry, metaphase fluorescence in situ hybridization, and chromosome analysis on 26 cases of diffuse large B-cell lymphoma (large noncleaved cell lymphoma). The gain or high-level amplification of 18q was found in eight tumors (31%) by CGH, and Southern analysis revealed BCL2 amplification in these cases, but not in the cases with normal chromosome 18 or t(14;18)(q32;q21). Western immunoblot analysis and immunohistochemistry revealed a high-level expression of BCL2 protein in the cases with BCL2 amplification and t(14;18)(q32;q21). However, translocation (14;18)(q32;q21) was not detected in any of the cases with BCL2 amplification. Therefore, our results suggest that amplification of the BCL2 gene is an important mechanism for BCL2 protein overexpression in diffuse large B-cell lymphoma.

Adult↗

PubMed1997

17q12-21 amplicon, a novel recurrent genetic change in intestinal type of gastric carcinoma: a comparative genomic hybridization study.

We studied DNA copy number changes in gastric cancer (GC) using comparative genomic hybridization (CGH) analysis on 35 resected gastric carcinomas (22 of the intestinal type and 13 of the diffuse type). Eighty-three percent of the cases showed DNA copy number changes. Gains were more common than losses (median of 3 and 1 in primary tumors of the intestinal and diffuse type, respectively). The most common gains were detected on 20q [46%; 12 intestinal type (55%) and four diffuse type (31%)], 8q [37%; 10 intestinal type (45%) and three diffuse type (23%)], and 17q12-21 [29%; all but one intestinal type (41%)]. The most frequent losses were detected on 18q [26%; all intestinal type (41%)] and on 4q [23%; all intestinal type (32%)]. High-level amplifications were observed in the intestinal type of tumors at 17q12-21 (three tumors), 20q (three tumors). 2q (one tumor), and 18q (one tumor). In the diffuse type, high-level amplification was detected once at 13q.

Adult↗

PubMed1997

Comparative genomic hybridization analysis of chromosomal changes occurring during development of acquired resistance to cisplatin in human ovarian carcinoma cells.

The genetic changes underlying the development of resistance to the platinum-containing drugs are poorly defined. We analyzed six resistant cell lines using comparative genomic hybridization (CGH) in order to screen and identify possible genetic changes in common. We compared parental 2008 and A2780 human ovarian cancer cells to sublines selected for resistance to cisplatin (DDP) (2008/C8, 2008/C13*5.25, 2008/A, A2780/CP); we also compared 2008 cells to sublines selected for resistance to antimonite (2008/H) and arsenite (2008/I) which demonstrated cross-resistance to DDP. DNA samples from the resistant cell lines were hybridized against DNA from the parental cells rather than from normal human cells to permit detection of only those changes associated with the development of resistance. The DNA sequence copy number changes were surprisingly numerous in the DDP, antimony, and arsenite-resistant variants of the 2008 cell line and most of the chromosomes were affected. On the other hand, in the A2780/CP subline only a few changes were found and these were limited to just four chromosomes. The most common findings among the DDP-resistant cell lines were gains of material from chromosomes or chromosome arms 2q (5 out of 6 lines), 4 (4/6), 6q (5/6), and 8q (4/6). Deletions were observed on chromosomes or chromosome arms 2p (4/6), X (4/6), 7p (5/6), 11p (4/6), and 13 (4/6). The most frequently involved chromosomal regions, affected in the majority of cell lines, were: gain of 2q14.1-q33, 4p15.2-p13, 4q22-q25, 4q31.1-q34, 6q13-q16, 8q12-q21.2, and loss of Xp22.2-q21, 7p21-p14, 11cen-p14 in sublines of 2008, and loss of 2pter-p22 and 13q21 in sublines of 2008 and A2780. The results suggest that the acquired resistance and cross-resistance to DDP in these cell lines was associated with substantial genomic instability, quite unlike the changes observed in association with the development of resistance to drugs participating in the multidrug resistance phenotype.

Chromosome Aberrations↗

PubMed1996

DNA copy number changes in diffuse large B-cell lymphoma--comparative genomic hybridization study.

We studied DNA copy number changes in diffuse large B-cell lymphoma using comparative genomic hybridization analysis on 20 primary tumors and on 12 recurrent tumors excised after chemotherapy or radiotherapy. Twenty-nine (91%) of the cases showed abnormal copy number karyotypes. Chromosomal regions at X (41%), 1q (38%), 7 (31%), 3 (24%), 6p (21%), 11 (21%), 12 (21%), and 18 (21%) were most frequently gained, and the most common losses involved 6q (38%), X (21%), 1p (14%), and 8p (10%). High-level amplifications were observed at 6p23-ter, 10p12-14, 17p1l.2, 18q21-ter, and Xq22-ter, all but 18q appearing only in the recurrent tumors. Gains (median, 2; range, 0 to 10) were more frequent than losses (median, 1; range, 0 to 7; P = .0004). The median number of aberrations found in the recurrent tumors (6.5) was greater than that in the primary tumors (2; P = .01). The copy number changes found in the recurrent tumors were more random than those found in the primary tumors, which were mainly located in the most frequently affected regions. Our findings are in line with those observed using conventional cytogenetic analysis, but especially novel high-level amplifications were detected. Southern blot analysis showed BCL2 amplification, but not translocation t(14;18)(q32;q21), in cases in which a gain at 18q was detected by comparative genomic hybridization, which strongly suggests that, in addition to translocation, gene amplification is another mechanism for the overexpression of the BCL2 protein.

Adult↗

PubMedDate not supplied

Causes and consequences of BCL2 overexpression in diffuse large B-cell lymphoma.

We investigated the frequency of bcl-2 protein overexpression in 80 diffuse large B-cell lymphoma (DLBCL) patients using both Western blotting and immunohistochemistry (IHC). Fifty-nine percent of the DLBCLs overexpressed bcl-2 protein by Western blot and 52% by IHC. The two methods usually gave concordant results (p=0.005), but 14 (21%) out of the 67 cases that were analyzed by both methods were positive by Western blot and negative by IHC, and 8 (12%) cases vice versa. Bcl-2 overexpression by IHC was associated with poor response to chemotherapy and poor survival, whereas these associations were not found when bcl-2 overexpression was determined by Western blotting. The molecular mechanisms leading to bcl-2 overexpression were evaluated by PCR, karyotype analysis, and comparative genomic hybridization (CGH). When studied by PCR and/or karyotype analysis, 12 (15%) of the 80 cases had translocation (14;18)(q32;q21). All 12 lymphomas with (14;18)(q32;q21) translocation had bcl-2 overexpression by Western blot as compared with 35 (51%) of the 68 lymphomas without translocation (p=0.001). Ten (29%) out of 34 cases that were analyzed by CGH showed amplification of chromosome 18 in which the BCL2 gene is located, and all cases showed bcl-2 overexpression by both Western blot and IHC. The results suggest that gene amplification and translocation are at least equally common mechanisms causing bcl-2 protein overexpression in DLBCL. Bcl-2 protein overexpression as determined by IHC is associated with poor response to chemotherapy and poor survival.

Adolescent↗