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688. |
- Höglund, Mattias, et al.
(författare)
-
Dissecting karyotypic patterns in colorectal tumors: two distinct but overlapping pathways in the adenoma-carcinoma transition.
- 2002
-
Ingår i: Cancer Research. - 1538-7445. ; 62:20, s. 5939-5954
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
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689. |
- Höglund, Mattias, et al.
(författare)
-
Identification of cytogenetic subgroups and karyotypic pathways in transitional cell carcinoma
- 2001
-
Ingår i: Cancer Research. - 1538-7445. ; 61:22, s. 8241-8246
-
Tidskriftsartikel (refereegranskat)abstract
- The clinical course in urinary bladder cancer is difficult or impossible to predict based on conventional disease parameters. It is a reasonable hypothesis that the genetic aberrations acquired by the tumor cells, being instrumental in bringing about the disease in the first place, may also hold the key to more reliable prognostication. However, though 200 transitional cell carcinomas (TCC), the most common bladder cancer in the Western world, with clonal chromosomal abnormalities have been reported, our knowledge about the karyotypic characteristics of these tumors remains insufficient. The aberration pattern is clearly nonrandom, but no completely specific primary or secondary karyotypic abnormality has been identified, and the chronological order in which the aberrations appear during disease progression is not well known. The high degree of karyotypic complexity in epithelial tumors like TCC is one reason why our picture of the sequential order of cytogenetic evolution is unclear. To overcome some of these difficulties we have used several statistical methods that allow analysis and interpretation of the relationship between cytogenetic aberrations in TCC. We show that there exists a temporal order with respect to the appearance of chromosomal imbalances and that this order is highly correlated with tumor stage and grade. Analyzing changes in the distribution of imbalances per tumor in G1, G2, and G3 tumors, we suggest that progression involves the acquisition of cytogenetically detectable and submicroscopic genetic changes at comparable frequencies. By means of computer simulations, we show that the imbalances -9, +7, and 1q+ appear earlier than expected from random events and that -6q, -5q, -18, +5p, -22p, and -15 appear later than expected. Using principal component analysis, we identify two cytogenetic pathways in TCC, one initiated by -9 and followed by -11p and 1q+, the other initiated by +7 and followed by 8p- and +8q. The -9 pathway was correlated with stage Ta-T2 tumors, whereas the +7 pathway was correlated with stage T1-T3 tumors, i.e., +7 tumors appeared to be more aggressive. Although these pathways are well separated at earlier stages, they later converge to contain a common set of imbalances.
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690. |
- Höglund, Mattias, et al.
(författare)
-
Multivariate analysis of chromosomal imbalances in breast cancer delineates cytogenetic pathways and reveals complex relationships among imbalances.
- 2002
-
Ingår i: Cancer Research. - 1538-7445. ; 62:9, s. 2675-2680
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
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