Genes Chromosomes and Cancer
1098-2264
1045-2257
Mỹ
Cơ quản chủ quản: WILEY , Wiley-Liss Inc.
Lĩnh vực:
Cancer ResearchGenetics
Phân tích ảnh hưởng
Thông tin về tạp chí
Genes, Chromosomes & Cancer will offer rapid publication of original full-length research articles, perspectives, reviews and letters to the editors on genetic analysis as related to the study of neoplasia. The main scope of the journal is to communicate new insights into the etiology and/or pathogenesis of neoplasia, as well as molecular and cellular findings of relevance for the management of cancer patients. While preference will be given to research utilizing analytical and functional approaches, descriptive studies and case reports will also be welcomed when they offer insights regarding basic biological mechanisms or the clinical management of neoplastic disorders.
Các bài báo tiêu biểu
Optimizing comparative genomic hybridization for analysis of DNA sequence copy number changes in solid tumors Abstract Comparative genomic hybridization (CGH) is a powerful new method for molecular cytogenetic analysis of cancer. In a single hybridization, CGH provides an overview of DNA sequence copy number changes (losses, deletions, gains, amplifications) in a tumor specimen and maps these changes on normal chromosomes. CGH is based on the in situ hybridization of differentially labeled total genomic tumor DNA and normal reference DNA to normal human metaphase chromosomes. After hybridization and fluorescent staining of the bound DNAs, copy number variations among the different sequences in the tumor DNA are detected by measuring the tumor/normal fluorescence intensity ratio for each locus in the target metaphase chromosomes. CGH is in particular useful for analysis of DNA sequence copy number changes in common solid tumors where high‐quality metaphase preparations are often difficult to make, and where complex karyotypes with numerous markers, double minutes, and homogeneously stained chromosomal regions are common. CGH only detects changes that are present in a substantial proportion of tumor cells (i.e., clonal aberrations). It does not reveal translocations, inversions, and other aberrations that do not change copy number. At present, CGH is a research tool that complements previous methods for genetic analysis. CGH will advance our understanding of the genetic progression of cancer and highlight important genomic regions for further study. Direct clinical applications of CGH are possible, but will require further development and validation of the technique. We describe here our recent optimized procedures for CGH, including DNA labeling, hybridization, fluorescence microscopy, digital image analysis, data interpretation, and quality control, emphasizing those steps that are most critical. We will also assess sensitivity and resolution limits of CGH as well as discuss possible future technical improvements. Genes Chromosom Cancer 10:231–243 (1994). © 1994 Wiley‐Liss, Inc.
Tập 10 Số 4 - Trang 231-243 - 1994
Identification of amplified DNA sequences in breast cancer and their organization within homogeneously staining regions Abstract A modified comparative genomic hybridization (mCGH) technique was used to identify and map amplified DNA sequences in six homogeneously staining regions (hsr) from three primary breast carcinomas. Five different chromosomal regions and bands were identified as sites of amplification: 8p1, 17q21.1, 17q23 (two cases), 19q13.3, and 20q13.3. The mCGH site located on 17q21.1 was demonstrated to correspond to a 50–100‐fold amplification of ERBB2. Further in situ hybridization experiments were used to confirm the mCGH results and to characterize the organization of the amplified sequences within the hsr. In five of six instances, two or more chromosomal regions were found amplified in the same hsr. In the tumor with the less modified karyotype, the two hsr comprised DNA sequences from three different chromosomes and showed different patterns of amplification. In the tumor with the most rearranged karyotype, the hsr‐carrying chromosomes were formed by the translocation and amplification of sequences from three or four different chromosomal sites. This illustrates the complexity of the amplification process in breast cancers.
Tập 14 Số 3 - Trang 155-163 - 1995
<i>FGFRI</i> and <i>PLAT</i> genes and DNA amplification at 8p 12 in breast and ovarian cancers Abstract Several chromosomal regions are found to be consistently amplified in human breast cancers. For two of these regions, 8p 12 and 10q26, we previously reported the amplification of genes encoding FGF receptors, FGFR1/FLG and FGFR2/BEK , in about 12% of breast tumors. The PLAT gene, encoding the tissue‐type plasminogen activator, is also located close to or within the 8p 12 region. In the present study, we show that both FGFR1 and PLAT can be amplified in breast as well as ovarian carcinomas. FGFR1 amplification was detected in 14.5% of breast and 7.8% of ovarian tumors, whereas PLAT was found to be amplified in 15.6% and 19.4% of the tumors, respectively. Each gene could be amplified independently of the other. These data raised the question of which gene is selected for amplification at 8p 12. In most cases, the levels of expression of FGFR1 and PLAT in breast tumors were comparable to their level of expression in normal mammary tissue. However, FGFR1 was expressed above the normal level in a certain number of cases. This gene could be a good candidate as “driver” of the 8p 12 amplification, but it cannot account for all complex molecular events taking place in this region. © 1993 Wiley‐Liss, Inc.
Tập 7 Số 4 - Trang 219-226 - 1993
Chromosome analysis of 97 primary breast carcinomas: Identification of eight karyotypic subgroups Abstract Chromosome banding analysis of 97 short‐term cultured primary breast carcinomas revealed clonal aberrations in 79 tumors, whereas 18 were karyotypically normal. In 34 of the 79 tumors with abnormalities, two to eight clones per case were detected; unrelated clones were present in 27 (34%) cases, whereas only related clones were found in seven. These findings indicate that a substantial proportion of breast carcinomas are of polyclonal origin. Altogether eight abnormalities were repeatedly identified both as sole chromosomal anomalies and as part of more complex karyotypes: the structural rearrangements i(1)(q10), der(1;16)(q10;p10), del(1)(q11–12), del(3)(p12–13p14–21), and del(6)(q21–22) and the numerical aberrations +7, +18, and +20. At least one of these changes was found in 41 (52%) of the karyotypically abnormal tumors. They identify a minimum number of cytogenetic subgroups in breast cancer and are likely to represent primary chromosome anomalies in this type of neoplasia. Other candidates for such a role are translocations of 3p12–13 and 4q21 with various partner chromosomes and inversions of chromosome 7, which also were seen repeatedly. Additional chromosomal aberrations that give the impression of occurring nonrandomly in breast carcinomas include structural rearrangements leading to partial monosomies for 1p, 8p, 11p, 11q, 15p, 17p, 19p, and 19q and losses of one copy of chromosomes X, 8, 9, 13, 14, 17, and 22. The latter changes were seen consistently only in complex karyotypes, however, and we therefore interpret them as being secondary anomalies acquired during clonal evolution.
Tập 12 Số 3 - Trang 173-185 - 1995
Detection of DNA amplification in 17 primary breast carcinomas with homogeneously staining regions by a modified comparative genomic hybridization technique Abstract A modified comparative genomic hybridization (mCGH) technique was applied to a series of 17 primary breast carcinomas in which cytogenetic study (CG) demonstrated the presence of homogeneously staining region(s), suggesting the occurrence of DNA amplification. mCGH demonstrated recurrent amplifications of the whole chromosome arms 8q (9 times) and I q (7 times) and of DNA loci in the following bands: 11 q 13 (6 times), 9p 13 and 17q21.1 (4 times), I q21.1 and 16p 11.2 (3 times), and 8q22, 8q24.1, 10q22, 15q26, 17q23, and 20q 13.3 (twice). Amplification of whole chromosome arms is likely to have resulted from unbalanced translocations or isochromosomes, whereas amplifications of smaller chromosomal segments probably arose through real DNA amplification processes. In all tumors but one, more than one amplified locus was detected. The fact that many chromosomal sites were involved suggests that the process of amplification is complex and that many genes are potential targets. Genes Chromosom Cancer 10:160–170 (1994). © 1994 Wiley‐Liss, Inc.
Tập 10 Số 3 - Trang 160-170 - 1994
Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: Identification of candidate amplified and overexpressed genes Abstract Cervical cancer (CC) cells exhibit complex karyotypic alterations, which is consistent with deregulation of numerous critical genes in its formation and progression. To characterize this karyotypic complexity at the molecular level, we used cDNA array comparative genomic hybridization (aCGH) to analyze 29 CC cases and identified a number of over represented and deleted genes. The aCGH analysis revealed at least 17 recurrent amplicons and six common regions of deletions. These regions contain several known tumor‐associated genes, such as those involved in transcription, apoptosis, cytoskeletal remodeling, ion‐transport, drug metabolism, and immune response. Using the fluorescence in situ hybridization (FISH) approach we demonstrated the presence of high‐level amplifications at the 8q24.3, 11q22.2, and 20q13 regions in CC cell lines. To identify amplification‐associated genes that correspond to focal amplicons, we examined one or more genes in each of the 17 amplicons by Affymetrix U133A expression arrays and semiquantitative reverse‐transcription PCR (RT‐PCR) in 31 CC tumors. This analysis exhibited frequent and robust upregulated expression in CC relative to normal cervix for genes EPHB2 (1p36), CDCA8 (1p34.3), AIM2 (1q22‐23), RFC4 , MUC4 , and HRASLS (3q27‐29), SKP2 (5p12‐13), CENTD3 (5q31.3), PTK2, RECQL4 (8q24), MMP1 and MMP13 (11q22.2), AKT1 (14q32.3), ABCC3 (17q21‐22), SMARCA4 (19p13.3) LIG1 (19q13.3), UBE2C (20q13.1), SMC1L1 (Xp11), KIF4A (Xq12), TMSNB (Xq22), and CSAG2 (Xq28). Thus, the gene dosage and expression profiles generated here have enabled the identification of focal amplicons characteristic for the CC genome and facilitated the validation of relevant genes in these amplicons. These data, thus, form an important step toward the identification of biologically relevant genes in CC pathogenesis. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045‐2257/suppmat . © 2007 Wiley‐Liss, Inc.
Tập 46 Số 4 - Trang 373-384 - 2007
Atypical mRNA fusions in <i>PML‐RARA</i> positive, <i>RARA‐PML</i> negative acute promyelocytic leukemia Abstract Reciprocal RARA‐PML transcripts are not detected in ∼25% of patients with PML‐RARA positive acute promyelocytic leukemia (APL), but the reasons for this are poorly understood. We studied 21 PML‐RARA positive/RARA‐PML negative cases by bubble PCR and multiplex long template PCR to identify the genomic breakpoints. Additional RT‐PCR analysis was performed based on the DNA findings. Three cases were found to have complex rearrangements involving a third locus: the first had a PML‐CDC6‐RARA forward DNA fusion and expressed a chimeric PML‐CDC6‐RARA mRNA in addition to a PML‐RARA . The other two had HERC1‐PML and NT_009714.17‐PML genomic fusion sequences at their respective reciprocal breakpoints. Six patients were falsely classified as RARA‐PML negative due to deletions on chromosome 15 and/or 17, or alternative splicing leading to atypical RARA‐PML fusion transcripts, which were not identified by conventional RT‐PCR assays. This study demonstrates that the frequency of RARA‐PML expression has been underestimated and highlights remarkable complexity at chromosomal breakpoint regions in APL even in cases with an apparently simple balanced t(15;17)(q24;q12). © 2010 Wiley‐Liss, Inc.
Tập 49 Số 5 - Trang 471-479 - 2010
Most gene fusions in cancer are stochastic events Abstract Cancer‐associated gene fusions resulting in chimeric proteins or aberrant expression of one or both partner genes are pathogenetically and clinically important in several hematologic malignancies and solid tumors. Since the advent of different types of massively parallel sequencing (MPS), the number of identified gene fusions has increased dramatically, prompting the question whether they all have a biologic impact. By ascertaining the chromosomal locations of 8934 genes involved in 10 861 gene fusions reported in the literature, we here show that there is a highly significant association between gene content of chromosomes and chromosome bands and number of genes involved in fusions. This strongly suggests that a clear majority of gene fusions detected by MPS are stochastic events associated with the number of genes available to participate in fusions and that most reported gene fusions are passengers without any pathogenetic importance.
Tập 58 Số 9 - Trang 607-611 - 2019
Deletion mapping on the long arm of chromosome 7 in splenic lymphoma with villous lymphocytes Abstract Splenic lymphoma with villous lymphocytes (SLVL) is a low‐grade lymphoproliferative disorder characterized by splenomegaly and circulating villous lymphocytes in the peripheral blood. It is considered to be the leukemic form of splenic marginal zone lymphoma (SMZL). The genetic basis of this lymphoma type remains unknown. Conventional cytogenetic studies have identified frequent structural abnormalities of chromosome 7, in the form of translocations, mainly unbalanced, and 7q deletions. In this current study, we undertook deletion mapping of the long arm of chromosome 7 in a series of cases with SLVL. Metaphase fluorescence in situ hybridization (FISH) was used in the first instance, followed by a study of loss of heterozygosity (LOH). The common area of deletion identified by FISH spanned from the YAC clone HSC7E1289 (mapping to 7q32.1) to in between YACs HSC7E195 and HSC7E648 (7q32–3). By application of 50 microsatellite markers mapping to the FISH‐CDR and to areas of deletion reported in other studies, four distinct hotspot loci were identified, with abnormalities present in 29–55% cases. In three of them, both LOH and biallelic deletions were found. The LOH in the majority of patients was noncontiguous. The presence of a high incidence of abnormalities in the established hotspot areas and in particular the finding of biallelic deletions is indicative of the existence of genes important for the pathogenesis of SLVL in these areas. © 2002 Wiley‐Liss, Inc.
Tập 36 Số 1 - Trang 57-69 - 2003
Gene expression and single nucleotide polymorphism array analyses of spindle cell lipomas and conventional lipomas with 13q14 deletion Abstract Spindle cell lipomas (SCL) are circumscribed, usually s.c. tumors that typically occur on the posterior neck, shoulder, and back of middle aged men. Cytogenetically, almost all SCL are characterized by deletions of chromosome arm 13q, often in combination with loss of 16q. Deletions of 13q are seen also in approximately 15% of conventional lipomas. Through single nucleotide polymorphism (SNP) array analyses, we identified two minimal deleted regions (MDR) in 13q14 in SCL. In MDR1, four genes were located, including the tumor suppressor gene RB1 . MDR1 in SCL overlapped with the MDR detected in conventional lipomas with 13q14 deletion. In MDR2 in SCL there were 34 genes and the two microRNA (miRNA) genes miR‐15a and miR‐16‐1 . Global gene expression analysis was used to study the impact of the deletions on genes mapping to the two SCL‐associated MDR. Five genes (C13orf1 , DHRS12 , ATP7B , ALG11 , and VPS36 ) in SCL and one gene (C13orf1 ) in conventional lipomas with 13q‐deletions were found to be significantly underexpressed compared with control tissues. Quantitative real‐time PCR showed that miR‐16‐1 was expressed at lower levels in SCL than in the control samples. No mutations were found at sequencing of RB1 , miR‐15a , and miR‐16‐1 . Our findings further delineate the target region for the 13q deletion in SCL and conventional lipomas and show that the deletions are associated with down‐regulated expression of several genes, notably C13orf1 , which was the only gene to be significantly down‐regulated in both tumor types. © 2011 Wiley‐Liss, Inc.
Tập 50 Số 8 - Trang 619-632 - 2011