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Multivariate analyses of genomic imbalances in solid tumors reveal distinct and converging pathways of karyotypic evolution

In English

Författare

Summary, in English

A total of 3,016 malignant solid tumors (kidney, colorectal, breast, head and neck, ovarian, and lung carcinomas, neuroglial tumors, malignant melanoma, and testicular germ cell tumors) were selected for statistical analyses regarding karyotypic evolution. Genomic imbalances, i.e., net gains and losses, present in more than 5% of each tumor type were identified. Individual tumors were then classified with respect to absence or presence of these imbalances. To analyze for possible patterns of correlated imbalances, principal component analyses (PCA) were performed. Furthermore, algorithms were developed to analyze the temporal order of the imbalances, as well as the possible selection for early or late appearance in the karyotypic evolution. By analyzing the temporal order of imbalances common to many tumor types, a general order for nine of these emerged, namely, +7, -3p, -6q, -1p, -8p, -17p, -9p, -18, and -22. The distributions of the number of imbalances per case revealed a geometrical distribution, ranging from one to nine imbalances per tumor, in the majority of the tumor types. In tumor types in which cases with a high number of imbalances per case were frequent, notably head and neck, ovarian, and lung carcinomas, the overall distributions were bimodal, indicating the presence of two modes of chromosome evolution. By combining data from the PCA with the temporal analyses, it was possible to identify karyotypic pathways. It was found that the majority of the tumor types displayed more than one cytogenetic route, but, as the karyotypic evolution continued, these converged to a common pathway.

Avdelning/ar

Publiceringsår

2001

Språk

Engelska

Sidor

156-171

Publikation/Tidskrift/Serie

Genes, Chromosomes and Cancer

Volym

31

Issue

2

Dokumenttyp

Artikel i tidskrift

Förlag

John Wiley & Sons Inc.

Ämne

  • Medical Genetics

Status

Published

Forskningsgrupp

  • Evolutionary Genetics

ISBN/ISSN/Övrigt

  • ISSN: 1045-2257