Biomedical subjects

Gunnar B Hansen

Publications and source records attributed to Gunnar B Hansen.

9 recordsLinked to original sources

PubMed2004

Statistical dissection of cytogenetic patterns in lung cancer reveals multiple modes of karyotypic evolution independent of histological classification.

Lung carcinomas are cytogenetically highly complex. In spite of this, patterns of recurrent chromosome aberrations have emerged. Apart from the frequent loss of 3p, losses of 4q, 5q, 8p, 9p, 10q, 13q, and 17p are common and gains often include 1q, 3q, 5p, and 8q. In the present study, we retrieved all aberrant lung carcinoma karyotypes, in total 432 cases, from the Mitelman Database of Chromosome Aberrations in Cancer and identified the most frequent imbalances. Each case was then classified with respect to the presence or absence of these imbalances and the data were statistically analyzed by means of principal component analysis, multidimensional scaling, and hierarchical cluster analysis. The analyses suggest that lung cancer develops through three pathways, initiated by +7, 3p-, and +12, respectively, and that the 3p- pathway is dominated by losses and the +12 pathway by gains. Gain of chromosome 7 was shown to be both important in the 3p- pathway and also forming a group of tumors containing +7 and +20 (with few additional changes). The distribution of the number of imbalances per tumor indicated that the karyotypic evolution might pass through three different phases. Phase I is characterized by tumors with few changes and by well-separated 3p- and +12 pathways. Phase II cases have an increased number of imbalances and exhibit less distinct 3p- and +12 pathways. Phase III tumors are polyploid and highly complex. No marked differences between the karyotypic profiles were found among morphologic subtypes, suggesting that lung cancer morphology is independent of the particular cytogenetic pathway operating in the tumor cells.

Adenocarcinoma↗

PubMed2004

Statistical analyses of karyotypic complexity in head and neck squamous cell carcinoma.

More than 250 head and neck squamous cell carcinomas (HNSCCs) with clonal chromosomal abnormalities have been reported. Even though the pattern of aberrations is nonrandom, no specific primary or secondary karyotypic abnormalities have been identified. One explanation for the still-rudimentary understanding of the cytogenetic evolution in HNSCC could be the pronounced karyotypic complexity seen in these tumors. In an attempt to overcome this difficulty, we have applied several statistical methods such as hierarchical cluster analysis, multidimensional scaling, and k-means clustering, which allow the identification and interpretation of karyotypic pathways, as well as establishing a temporal order of chromosomal imbalances on 241 published and 70 previously unpublished HNSCC karyotypes. From the analysis of the distribution of the number of imbalances per tumor we suggest that the carcinomas evolve through three phases representing different stages of chromosomal instability. Two major cytogenetic pathways, one dominated by gains and another by losses, were identified by means of principal component analysis. These were initiated by +7 and by any of the aberrations 1p-, 3p-, or 7q-, respectively.

Allelic Imbalance↗

PubMed2004

Wilms tumors develop through two distinct karyotypic pathways.

Wilms tumor is an embryonic neoplasm characterized by a large variation in histologic patterns. Cytogenetic investigations have identified nonrandom chromosomal changes characteristic for this tumor type, of which numerical changes, mostly trisomies for chromosomes 7, 8, and 12, are particularly frequent. Despite the abundance of cytogenetic information, with more than 350 published karyotypes, very little is known about the mode of karyotypic evolution. In this investigation, we have used 355 karyotypes of Wilms tumor to identify frequent imbalances. The most frequent were +1q, +6, +7q, +8, +12, +13, -11, and -16. Tumor cases were then classified with respect to the presence or absence of these imbalances and statistically analyzed to assess the order of appearance of chromosomal imbalances, as well as possible karyotypic pathways. We show that Wilms tumors develop through one major mode of karyotypic evolution, common to both low- and high-complex tumors, and that polyploid cases are relatively rare. We also establish a temporal order by which the different imbalances occur and show that at least two cytogenetic pathways exist, one dominated by gains and another by losses. We also show that these pathways are well separated and do not share a common set of late imbalances.

Biological Evolution↗

PubMed2004

Dissecting karyotypic patterns in malignant melanomas: temporal clustering of losses and gains in melanoma karyotypic evolution.

Malignant melanomas can be divided into two major subtypes, involving either the skin or eye melanomas. Both tumor forms exhibit highly complex karyotypes with nonrandom recurrent chromosomal imbalances. Loss of chromosome 3, the short arm of chromosome 1, and gain of 8q have been suggested to be associated with eye melanomas, whereas gain of 6p and loss of 6q have been more often seen in skin melanomas. Imbalances implicated in tumor progression include among others, -10 and +7. In spite of the abundance of cytogenetic information, with more than 300 published karyotypes, very little is known about the mode of karyotypic evolution or of the presence of possible cytogenetic pathways. In our investigation, we have used 362 melanoma karyotypes, including both the skin and eye subtypes, to identify the most frequently occurring imbalances. Tumor cases were then classified with respect to the presence or absence of these imbalances and statistically analyzed in order to assess the order of appearance of chromosomal imbalances, the presence of karyotypic pathways, as well as possible cytogenetic subtypes. We show that the melanomas develop through one mode of karyotypic evolution, common to both low and high complexity karyotypes, and we establish the temporal order by which the different imbalances occur. By applying several statistical methods, we show that at least two cytogenetic pathways of clonal evolution exist in malignant melanomas, one initiated with -3 and one with +6p, and that these pathways operate in both skin and eye melanomas.

Chromosome Aberrations↗

PubMed2004

A model for karyotypic evolution in testicular germ cell tumors.

Testicular germ cell tumor karyotypes are characterized by near-triploidy, with chromosome numbers ranging from 50 to 70, and by the frequent appearance of i(12p). The high chromosome number has been attributed to the formation of tetraploid carcinoma in situ cells followed by chromosomal losses that ultimately lead to tumor forms that are more advanced. In the present investigation, we show by analysis of the accumulated cytogenetic data on testicular germ cell tumors and computer simulations that two distinct processes are operating in the karyotypic evolution of these tumors. The results suggest that whole-chromosome changes originate from a multipolar cell division of a tetraploid cell, whereas imbalances caused by structural changes accumulate in a stepwise manner.

Cell Division↗

PubMed2004

Dissecting karyotypic patterns in renal cell carcinoma: an analysis of the accumulated cytogenetic data.

Renal cell carcinoma (RCC) is one of the most frequent malignancies in Western societies. The most common subtypes are conventional (clear-cell) and papillary carcinomas, which account for about 75 and 10% of cases, respectively. Cytogenetically, conventional RCC is the best-studied subtype and is characterized by chromosomal losses: loss of the short arm of chromosome 3 being the most common. Papillary tumors frequently show gains of chromosomes 7 and 17, and the more progressed forms have, in addition, gains of chromosomes 16, 12, and 20. In the present investigation we used 796 RCC karyotypes to identify the most frequent genomic imbalances. Tumor cases were then classified with respect to the presence or absence of these imbalances and statistically analyzed to assess the order of appearance of chromosomal imbalances, as well as possible karyotypic pathways and cytogenetic subtypes. We established a temporal order by which the different imbalances occur and showed that at least two cytogenetic pathways exist in RCC, one hypodiploid characterized by presence of 3p- and one hyperdiploid characterized by the presence of +7. The data suggest that conventional-type tumors predominantly evolve through the hypodiploid pathway but that an alternative route may be by hyperdiploidy if 3p- is present. Tumors with a papillary growth pattern predominantly progress through the hyperdiploid pathway. The analyses also revealed three possible cytogenetic subtypes of the papillary tumors, one characterized by the presence of +10, a second by +17 and +3q, and a third by +16, +20, and +12.

Adenocarcinoma↗

PubMed2003

Ovarian carcinoma develops through multiple modes of chromosomal evolution.

Ovarian carcinoma has the highest mortality of all of the gynecologic cancers. The chromosomal changes in this tumor type are highly complex, and the karyotypes typically show severe aneuploidy. Despite the abundance of cytogenetic information, with approximately 400 published karyotypes, very little is known about the mode of karyotypic evolution and the possible presence of cytogenetic pathways related to tumor development. In the present investigation we used 387 ovarian carcinoma karyotypes to identify the most frequent genomic imbalances. Tumor cases were then classified with respect to the presence or absence of these imbalances and statistically analyzed to assess the order of appearance of chromosomal imbalances, as well as possible karyotypic pathways and cytogenetic subtypes. We establish the temporal order by which the different imbalances occur and show that at least two cytogenetic pathways exist, one characterized by +7, +8q, and +12, and one by 6q- and 1q-. We show that ovarian carcinomas develop through at least three phases of karyotypic evolution. At the early stages, Phase I, the karyotypic evolution seems to proceed though step-wise acquisition of changes. The transition to Phase II showed signs of an increased chromosomal instability, most probably caused by extensive telomere crisis and the onset of breakage-fusion-bridge cycles. This process was linked to the presence of imbalances characteristic for the 6q-/1q- pathway. The transition to Phase III involved triploidization and was also linked to the presence of the 6q-/1q- pathway.

Allelic Imbalance↗

PubMed2002

Dissecting karyotypic patterns in colorectal tumors: two distinct but overlapping pathways in the adenoma-carcinoma transition.

More than 500 colorectal tumors with clonal chromosomal abnormalities have been reported. Although the pattern of aberrations is nonrandom, no specific primary or secondary karyotypic abnormality has been identified. Also, the chronological order in which the aberrations appear during disease progression is not well known. One reason why our understanding of the cytogenetic evolution is unclear is the high degree of karyotypic complexity seen in these tumors. To overcome some of these difficulties we have previously used several statistical methods that allow identification and interpretation of karyotypic pathways as well as establishment of a temporal order of appearance of the imbalances. These methods were applied on 531 colorectal tumor karyotypes. By using a resampling strategy, 1p-, +7, 7q-, and +12p were identified as early events. Two major and two minor cytogenetic pathways were identified by means of principal component analysis. The two major pathways were initiated with 1p- and +7, and the minor pathways were initiated with +12p and 7q-. The +7/+12p tumors were found to be hyperdiploid, whereas those with 1p-/7q- were pseudodiploid. We also show that the adenoma-carcinoma transition in the 1p- pathway is strongly linked to karyoytypic evolution, whereas the +7 pathway is not, and that the cytogenetic pathways are separated at both early and late stages.

Adenoma↗

PubMed2002

Multivariate analysis of chromosomal imbalances in breast cancer delineates cytogenetic pathways and reveals complex relationships among imbalances.

More than 550 breast adenocarcinomas with clonal chromosomal abnormalities have been reported. Although the aberration pattern is clearly nonrandom, no specific primary or secondary karyotypic abnormality has been identified, and furthermore the chronological order in which the aberrations appear during disease progression is not well known. The high degree of karyotypic complexity in epithelial tumors such as breast cancer is one reason why our understanding of the sequential order of cytogenetic evolution is unclear. To overcome some of these difficulties, we have used several statistical methods that allow identification and interpretation of karyotypic pathways. These methods were applied on 538 breast cancer karyotypes. The distribution of the number of imbalances/tumor showed a monomodal appearance, indicating that one single mode of karyotypic evolution is operating in this tumor type. We show that there exists a temporal order with respect to the appearance of chromosomal imbalances. The imbalances +1pq, 1q-, 3p-, and +7 appear earlier than expected from random events, and two cytogenetic pathways, one initiated by +1q and followed by 11q- and -22, the other initiated by either 3p- or 1q- and followed by 1p-, 3q-, and 6q-, can be discerned. We also show that +7 and +8q behave independently of the other imbalances and cannot, by simple means, be incorporated in the identified pathway scheme. Although the cytogenetic pathways are well separated at earlier stages, they later converge and include a common set of late imbalances.

Adenocarcinoma↗