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F Mertens

Publications and source records attributed to F Mertens.

At least 73 records · Page 4Linked to original sources
PubMed1999

Hibernomas are characterized by homozygous deletions in the multiple endocrine neoplasia type I region. Metaphase fluorescence in situ hybridization reveals complex rearrangements not detected by conventional cytogenetics.

Hibernomas are benign tumors of brown fat, frequently characterized by aberrations of chromosome band 11q13. In this study, the chromosome 11 changes in five hibernomas were analyzed in detail by metaphase fluorescence in situ hybridization. In all cases, complex rearrangements leading to loss of chromosome 11 material were found. Deletions were present not only in those chromosomes that were shown to be rearranged by G-banding, but in four cases also in the ostensibly normal homologues, resulting in homozygous loss of several loci. Among these, the gene for multiple endocrine neoplasia type I (MEN1) was most frequently deleted. In addition to the MEN1 deletions, heterozygous loss of a second region, approximately 3 Mb distal to MEN1, was found in all five cases, adding to previous evidence for a second tumor suppressor locus in 11q13.

Adult↗
PubMed1999

Correlation between clinicopathological features and karyotype in spindle cell sarcomas. A report of 130 cases from the CHAMP study group.

Soft-tissue tumors have proved to be a fruitful area for the identification of reproducible cytogenetic aberrations, especially among pediatric round-cell sarcomas and lipomatous tumors. Thus far, however, data regarding sarcomas of monomorphic spindle cell type have been limited and somewhat disappointing, with the notable exception of synovial sarcoma. As part of an ongoing international collaborative study, 130 karyotyped spindle-cell sarcomas were reviewed and classified histologically, without knowledge of the clinical and karyotypic data, with the aim of identifying objective correlations between morphology, karyotype, and clinical parameters. Clonal chromosomal abnormalities were identified in 82 cases studied (63%), but only in the group of synovial sarcomas was there clear correlation between the cytogenetic findings, in the form of a consistent t(X;18)(p11;q11), and morphology. Among leiomyosarcomas (41 cases) and malignant peripheral nerve sheath tumors (MPNSTs; 27 cases) as well as in individual examples of rarer entities, there was a general tendency for karyotypic complexity associated with frequent loss or rearrangement of chromosome arms 1p, 10p, 11q, 12q, 17p, and 22q. Rearrangements of 17q (the region of the NF1 gene) were seen in 9/27 (33%) of MPNSTs. Among nine cases of solitary fibrous tumor (in which previous cytogenetic data are very limited) no consistent aberrations were identified. We conclude that, with the exception of synovial sarcoma, most spindle-cell sarcomas share with pleomorphic sarcomas the tendency for karyotypic complexity. There was no indication (in most of these lesions) that detectable cytogenetic aberrations could either facilitate their diagnosis or help to determine prognosis. There is a clear need to further study and understand the significance of multiple chromosomal abnormalities in this group of mesenchymal neoplasms with the particular goal of determining their role in the process of tumor development.

Adolescent↗
PubMed1999

Clinical significance of genetic imbalances revealed by comparative genomic hybridization in chondrosarcomas.

DNA copy number changes were studied by comparative genomic hybridization (CGH) in 50 chondrosarcoma samples from 45 patients. Mean number of genetic aberrations in primary tumors was 4.8 +/- 1.8. The most frequently gained regions were 20q12-qter (37%), 20q (32%), 8q24.1-qter (27%), 20p (24%), and 14q24-qter (24%). Losses were 5.5 times less frequent than gains and observed mainly at Xcen-q21, 6cen-q22, and 18cen-q11.2 (11% each). Recurrent and metastatic tumors showed a mean of 4.0 +/- 2.2 aberrations per sample. The most frequently gained regions were chromosome 7 (4 cases), 5q14-q32 (4 cases), 6p (3 cases), and 12q (3 cases). Losses of DNA sequences were 3.4 times less frequent than gains. Histological tumor grade was significantly associated with metastasis-free survival (P = .002) and overall survival (P = .003), being the strongest prognostic factor tested. A statistically significant correlation was found between gain at 8q24.1-qter and shorter overall survival (P = .01) but not with local recurrence or metastasis-free survival. Gain at 14q24-qter was associated with a trend to shorter overall survival (P = .05) but neither with an increased risk for local recurrence nor with metastasis-free survival. In a multivariate analysis, only the tumor grade associated with overall survival (P = .02). In a multivariate analysis together with the tumor grade, gain at 8q24.1-qter did not retain its significance (P = .44), indicating that this imbalance is not an independent prognostic factor.

Adult↗
PubMed1999

Multiple polysomies in breast carcinomas: preferential gain of chromosomes 1, 5, 6, 7, 12, 16, 17, 18, and 19.

Chromosome G-banding analysis of metaphase cells from 16 primary breast carcinomas revealed the presence of multiple polysomies in near-diploid as well as in polyploid cells. Chromosome 17 was preferentially gained in 7 tumors, followed in frequency by chromosomes 1, 12, and 19 (5 tumors each), and chromosomes 5, 6, 7, 16, and 18 (4 tumors each). Eleven of the 16 carcinomas had, apart from the clones exhibiting the numerical gains, other unrelated clones. Nine of these 11 cases had clones with structural chromosome aberrations, 5 of which had structural aberrations involving the short arm of chromosome 3. The biologic significance, if any, of this seemingly nonrandom coexistence of multiple polysomies with structural aberrations of 3p is at present not known. The pattern of numerical chromosome aberrations observed in the present study is comparable to previous results from fluorescence in situ hybridization (FISH) studies, with the use of centromeric probes on interphase cells. However, unlike FISH studies, which have been focused on chromosomes 1, 3, 7, 8, 11, 16, and 17, the cytogenetic results reveal that other chromosomes also may be nonrandomly gained as part of multiple polysomies in breast carcinomas. In addition, the tumors with multiple polysomies were generally of high histologic grade and with metastasis to axillary lymph nodes, suggesting that multiple wholechromosome gains may be a pathway of genetic evolution or progression or both in some breast carcinomas.

Adult↗
PubMed1999

Fluorescent in situ hybridisation (FISH) characterisation of pericentromeric breakpoints on chromosome 5 in head and neck squamous cell carcinomas.

Pericentromeric rearrangements, such as isochromosomes and whole-arm translocations, are frequently encountered in short-term cultures from head and neck squamous cell carcinomas (HNSCC). To characterise further the localisation of the breakpoints in such rearrangements, metaphase cells from seven HNSCC known to carry structural rearrangements of the pericentromeric region of chromosome 5 were investigated using fluorescent in situ hybridisation (FISH) techniques. With a whole chromosome painting probe it could be confirmed that all chromosome 5 rearrangements identified at cytogenetic analysis contained chromosome 5 material. By using a centromere-specific alpha satellite probe it could be shown, however, that cytogenetically identical derivative chromosomes had different breakpoints. Thus, we conclude that the results of the present investigation add further support to the hypothesis that the essential outcome of near-centromeric chromosome rearrangements is the creation of genomic imbalances, i.e. gain and/or loss of neoplasia-associated genes.

Aged↗
PubMed1999

Unique cytological features and chromosome aberrations in chondroid lipoma: a case report based on fine-needle aspiration cytology, histopathology, electron microscopy, chromosome banding, and molecular cytogenetics.

Chondroid lipoma is a rare, benign tumor that may mimic soft-tissue sarcoma clinically. Its histopathologic features may resemble hibernoma, myxoid liposarcoma, myxoid chondrosarcoma, and other lipomatous or chondroid neoplasms. In this study, a chondroid lipoma was analyzed by fine-needle aspiration cytology, histopathology, electron microscopy, chromosome banding, and metaphase fluorescence in situ hybridization. The results demonstrate that chondroid lipoma exhibits a characteristic pattern by fine-needle aspiration cytology, including a mixture of benign adipose tissue with lipoblastlike cells, and chondroblastlike cells with a fibrochondroid matrix. Cytogenetically, a three-way rearrangement between chromosomes 1, 2, and 5 was found, together with an 11;16 translocation with a breakpoint in 11q13, approximately 1 Mb proximal to the MEN1 region shown to be rearranged frequently in hibernoma. The presence of a karyotype of low complexity, but without any of the genetic aberrations characteristic for other types of soft-tissue tumors, indicate that chondroid lipoma develops along a unique pathogenetic pathway.

Adult↗
PubMed1999

Chromosomal aberrations in breast cancer: a comparison between cytogenetics and comparative genomic hybridization.

The analysis of chromosomal imbalances in solid tumors using comparative genetic hybridization (CGH) has gained much attention. A survey of the literature suggests that CGH is more sensitive in detecting copy number aberrations than is karyotyping, although careful comparisons between CGH and cytogenetics have not been performed. Here, we compared cytogenetics and CGH in 29 invasive breast cancers after converting the karyotypes into net copy number gains and losses. We found 15 tumors (56%) with a significant agreement between the two methods and 12 tumors (44%) where the methods were in disagreement (two cases failed CGH analysis). Interestingly, in 13 of the 15 tumors where the two methods were concordant, there was also a strong correlation between chromosome index and DNA index by flow cytometry. In the opposite situation, i.e., when chromosome and DNA indices were not matching, there was disagreement between cytogenetics and CGH in 10 of the 12 tumors. Of the discordant cases, all except one had a "simple" abnormal karyotype. Unresolved chromosomal aberrations (marker chromosomes, homogeneously staining regions, double minutes) could not completely explain the differences between CGH and karyotyping. A likely explanation for the discrepancies is that the methods analyzed different cell populations. Gains and losses found by CGH represented the predominant (often aneuploid) clone, whereas the abnormal, near-diploid karyotypes represented minor cell clone(s), which, for unknown reasons, had a growth advantage in vitro.

Aneuploidy↗
PubMed1999

Analysis of 35 cases of localized and diffuse tenosynovial giant cell tumor: a report from the Chromosomes and Morphology (CHAMP) study group.

The karyotypes of 44 specimens from 35 patients with localized (n = 19) or diffuse (n = 16) tenosynovial giant cell tumors were studied. The majority of cases in both categories (11 of 19 localized; 12 of 16 diffuse) displayed clonal chromosomal aberrations, with a complex karyotype in three cases and a simple chromosomal aberration in the others. No difference in the distribution of karyotypic abnormalities was found between the localized and diffuse form except for trisomies (usually of chromosomes 5 and/or 7), which were more frequent in the diffuse type. The short arm of chromosome 1 (1p11-13) was most frequently rearranged, with 7 of 11 localized and 7 of 12 diffuse lesions affected. These findings indicate that the localized and diffuse forms of tenosynovial giant cell tumor might represent two morphologic manifestations of the same entity. The high frequency of clonal chromosomal abnormalities, with a clustering of structural rearrangements to 1p11-13, suggests that this disease is most likely neoplastic in nature and paves the way to search for gene(s) that might be involved in its development.

Adolescent↗
PubMed1999

Abnormal cell cycle regulation in malignancy.

The cell cycle consists of an initial growth phase (G1), DNA replication (S), a gap phase (G2), and mitosis (M), after which the cell may differentiate or enter the resting state (G0). The cycle is driven by a number of positive and negative regulatory phosphorylation and dephosphorylation events, involving protein kinases, protein phosphatases, cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors, that ultimately impinge on the activity of transcription factors. Unreplicated or damaged DNA blocks the progression of the cell cycle at checkpoints, including a late G1 checkpoint regulated by the dephosphorylated retinoblastoma protein and a late G2 checkpoint regulated by the phosphorylation of cyclin-dependent kinase 1 complexed with cyclin B. Many cell cycle regulator genes may be considered proto-oncogenes or tumor suppressor genes, and point mutations, amplifications, deletions, or rearrangements involving their loci, particularly those in the "RB pathway," are associated with various tumors. A number of molecular techniques may be used to detect genomic alterations or posttranscriptional modifications, but immunohistochemistry remains the most common method to determine expression levels of a regulatory protein. Multivariate analysis of the usefulness in prognosis has been applied most often for the general proliferation antigen Ki-67.

Biomarkers, Tumor↗
PubMed1999

Rearrangement of the neoplasia-associated gene HMGIC in synovia from patients with osteoarthritis.

The occurrence of clonal chromosome aberrations in short-term cultures from synovia, osteophytes, and cartilage from patients with osteoarthritis (OA) was recently reported. Among these aberrations, a recurrent involvement of chromosome bands 12q13-15 in structural rearrangements was detected in both synovia and osteophytes. Chromosomal abnormalities of 12q13-15 are frequent among malignant and benign mesenchymal tumors, and it was recently demonstrated that the molecular target in these neoplasms is the HMGIC gene. In this study, we show by fluorescence in situ hybridization that HMGIC was disrupted by rearrangements of 12q15 in synovia from two patients with OA. The finding of HMGIC rearrangement in a lesion that is not traditionally regarded as neoplastic not only widens the spectrum of disorders that may be associated with altered function of this gene, but also provides further support for the notion that genetically rearranged cell populations are part of the OA process.

Aged↗
PubMed1999

Chromosome band 9p21 is frequently altered in malignant peripheral nerve sheath tumors: studies of CDKN2A and other genes of the pRB pathway.

Malignant peripheral nerve sheath tumors (MPNSTs) are frequently associated with the disease neurofibromatosis type 1. Only few recurrent cytogenetic changes have been reported, including rearrangements of the short arm of chromosome 9. By fluorescence in situ hybridization with a centromere 9 probe, and by allelic imbalance studies with seven 9p21-23 markers in nine familial and three sporadic MPNSTs, we found interstitial deletions that supported CDKN2A as a possible target gene. Nine MPNSTs showed aberrations of CDKN2A by Southern blot analyses, and in four of these, expression of CDKN2A could not be detected by Northern blot analysis. No mutations of CDKN2A were identified by sequencing of the coding region, and gene inactivation by promoter methylation was not found. In the 9p allelic imbalance studies, a novel allele was detected at one locus in one tumor. Analyses of additional markers (n = 8) excluded mismatch repair deficiency as an important mechanism in the genesis of these tumors. The tumors were analyzed further for alterations in other candidate cell cycle-associated genes. In total, 11/12 MPNSTs showed DNA changes in one or more of the genes CDKN2A, CDKN2B, RB1, CDK4, MDM2, and CCND2. The present study suggests that disruption of the pRB pathway is common in MPNST, and that dose reduction of CDKN2A is particularly frequent and contributes to MPNST development. Genes Chromosomes Cancer 26:151-160, 1999.

Adolescent↗
PubMed1998

Cytogenetic and fluorescence in situ hybridization characterization of chromosome 1 rearrangements in head and neck carcinomas delineate a target region for deletions within 1p11-1p13.

Cytogenetic analyses have revealed structural rearrangements of chromosome 1 in a large fraction of head and neck carcinomas (HNCA). These aberrations frequently affect chromosomal band 1p13 and the centromeric region, the latter often in the form of isochromosome i(1q) and whole-arm translocations. To delineate the critical region involved in rearrangements of proximal 1p, we have undertaken a more precise breakpoint mapping in 13 HNCAs, using metaphase fluorescence in situ hybridization with 11 yeast artificial chromosome (YAC) clones spanning 1p. All of the tumors had chromosome 1 changes at G-banding analyses. Fluorescence in situ hybridization showed that in almost all of the cases, at least one copy of chromosome 1 was affected by centromeric rearrangement. By the use of YAC clones mapped to juxtacentromeric regions and a centromere-specific alpha-satellite probe, we detected variable breakpoints in the whole-arm translocations. At the cytogenetic level, 1p13 rearrangements were frequent. However, molecular breakpoints within this band varied among the HNCAs tested. The lack of consistently rearranged chromosome segments indicates that the pathogenetically important consequence of 1p rearrangements in HNCAs is loss and/or gain of genes outside the breakpoint regions. In an assessment of the genomic imbalances, partial or complete overrepresentation of 1q was seen in eight cases. Loss of 1p material was also identified in eight cases; and in four of them, the deleted segments were too small to be discovered by G-banding analysis. The minimal overlapping deleted region was in the interval between YAC 959C4 (band p11-p12) and the centromere (p10). Our findings indicate that a target region potentially harboring tumor suppressor gene(s) crucial for HNCA is located within chromosomal bands 1p11-p13.

Centromere↗
PubMed1998

A case of dermatofibrosarcoma protuberans with a ring chromosome 5 and a rearranged chromosome 22 containing amplified COL1A1 and PDGFB sequences.

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous tumour of borderline malignancy, the cytogenetic features of which include the translocation t(17;22)(q22;q13) or, more commonly, supernumerary ring chromosomes containing material from 17q22 and 22q13. These rearrangements result in the COL1A1/PDGFB fusion gene. Here, we describe a case of DFSP displaying a ring chromosome 5 together with a large marker chromosome composed of chromosome 22 alphoid DNA, material from distal 12q and amplified COL1A1 and PDGFB sequences. This is the first case of DFSP with multiple copies of COL1A1 and PDGFB not confined to ring chromosomes, showing that DFSP is similar to other borderline malignant mesenchymal tumours, where rings and giant markers are alternative vehicles for amplified material.

Adolescent↗
PubMed1998

Cytogenetic findings in invasive breast carcinomas with prognostically favourable histology: a less complex karyotypic pattern?

Seventeen invasive primary breast carcinomas of histological types usually considered to be prognostically favourable (2 medullary, 3 papillary, 3 tubular, and 9 mucinous carcinomas) were analysed as part of an ongoing study of the cytogenetics of breast cancer. Thirteen of the tumours (7 mucinous, 2 medullary, 2 papillary, and 2 tubular carcinomas) showed clonal chromosome aberrations. Trisomy 7 and i(1q) were present as sole and recurrent aberrations in the mucinous tumours. The 2 tubular carcinomas and I papillary carcinoma had simple numerical changes only, whereas the second papillary tumour had a balanced translocation as the sole anomaly. Both medullary carcinomas had chromosome numbers in the triploid range, with clones displaying structural and numerical changes. Our data, especially when collated with information on previously published cases of mucinous, papillary, tubular, and medullary breast carcinomas, show that the former 3 histological types, in keeping with their recognised prognostic advantage, appear to exhibit relatively simple karyotypic changes, i.e., numerical aberrations, balanced translocations, and near-diploid chromosome numbers. Medullary carcinomas on the other hand, appear to have more complex karyotypes, similar to those described for the more common ductal and lobular subtypes of breast carcinoma.

Adenocarcinoma, Mucinous↗
PubMed1998

Characterization of a malignant eccrine poroma by cytogenetic and fluorescence in situ hybridization techniques.

We have cytogenetically and by fluorescence in situ hybridization (FISH) analyzed short-term cultures from a malignant eccrine poroma, a type of tumor in which chromosomal abnormalities have previously not been reported. Combining the results from G-banding and FISH, the karyotype was interpreted as 50,XX,t(3;11;12)(q21;p15;q15),+5,+7,+9, +9,t(12;22)(q13;q13),+del(12)(q15),der(15)t(3;15) (q23;p13),der(17)t(8;17)(q22;p13),-20,add(22)(q13).

Acrospiroma↗
PubMed1998

Comparison of chromosomal patterns with clinical features in 165 lipomas: a report of the CHAMP study group.

Soft tissue lipomatous tumors are morphologically heterogeneous. Various morphologic features are associated with specific chromosomal patterns and clinical features such as age, sex, and tumor site, location, and size. Simple lipomas are known to be karyotypically heterogeneous, but this has not been correlated with clinicopathological features. In 165 cases of solitary soft tissue lipoma, short-term cultures were analyzed cytogenetically. The karyotypes were divided into the following groups: normal karyotype; 12q13-15 aberrations; 6p rearrangements; 13q rearrangements, 8q11-13 aberrations; ring or giant marker chromosomes or both; other aberrations. The tumors were reexamined morphologically without knowledge of the karyotypic or clinical data. An abnormal chromosomal pattern was observed in 129 of 165 cases (78%): in 75 of 90 (83%) lipomas in the extremities and in 43 of 63 (68%) trunk wall lipomas. Chromosomal aberrations were present in 69 of 90 (77%) subcutaneous tumors and in 59 of 64 (80%) deep tumors. A normal karyotype was twice as frequent in tumors in patients under 30 years of age than in those from older individuals (6 of 16 vs. 30 of 149, 40% resp. 20%). Apart from the finding that normal karyotypes were more common in patients younger than 30 years, there was no significant association between cytogenetic pattern and patient sex or age or tumor localization, size, or depth. The pathogenetic basis and clinicopathologic relevance (if any) of the cytogenetic subtypes among benign lipomas remain unexplained.

Adolescent↗