Comparative genomic hybridization reveals a specific pattern of chromosomal gains and losses during the genesis of colorectal tumors

Comparative genomic hybridization was used to screen the DNA extracted from histologically defined tissue sections from consecutive stages of colorectal carcinogenesis for chromosomal aberrations. No aberrations were detected in normal epithelium (n = 14). Gain of chromosome 7 occurred as a single event in low‐grade adenomas (n = 14). In high‐grade adenomas (n = 12), an overrepresentation of chromosomes 7 and 20 was present in 30% of the cases analyzed. The transition to colon carcinomas (n = 16) was characterized by the emergence of multiple chromosomal aberrations. Chromosomes 1, 13, and 20 and chromosome arms 7p and 8q were frequently gained, whereas chromosome 4 and chromosome arms 8p and 18q were recurrently underrepresented. The same tissue sections that were used for CGH were analyzed by means of DNA‐ploidy measurements and immunohistochemical staining to quantify proliferative activity and p21/WAF‐I and TP53 expression. We observed that crude aneuploidy and increased proliferative activity are early events in colorectal carcinogenesis, followed by TP53 overexpression and the acquisition of recurrent chromosomal gains and losses during the progression from high‐grade adenomas to invasive carcinomas. Genes Chromosom Cancer (1996). © 1996 Wiley‐Liss, Inc.

[1]  A. Zetterberg,et al.  Comparative genomic hybridization of formalin-fixed, paraffin-embedded breast tumors reveals different patterns of chromosomal gains and losses in fibroadenomas and diploid and aneuploid carcinomas. , 1995, Cancer research.

[2]  G. Auer,et al.  DNA ploidy in human colorectal adenocarcinomas. , 1993, Analytical and quantitative cytology and histology.

[3]  D. Ledbetter,et al.  Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. , 1989, Science.

[4]  Margaret Robertson,et al.  Identification and characterization of the familial adenomatous polyposis coli gene , 1991, Cell.

[5]  S. Jhanwar,et al.  Recurrent deletions involving chromosomes 1, 5, 17, and 18 in colorectal carcinoma: possible role in biological and clinical behavior of tumors. , 1995, Anticancer research.

[6]  L. Foulds,et al.  The natural history of cancer. , 1958, Journal of chronic diseases.

[7]  A. Andrén-sandberg,et al.  Cytogenetic analysis of 52 colorectal carcinomas‐‐non‐random aberration pattern and correlation with pathologic parameters , 1993, International journal of cancer.

[8]  S. Altschul,et al.  Identification of FAP locus genes from chromosome 5q21. , 1991, Science.

[9]  G. Auer,et al.  DNA ploidy in human colorectal adenomas. , 1994, Analytical and quantitative cytology and histology.

[10]  A. Andrén-sandberg,et al.  Cytogenetic aberrations in colorectal adenocarcinomas and their correlation with clinicopathologic features , 1993, Cancer.

[11]  Kathleen R. Cho,et al.  Identification of a chromosome 18q gene that is altered in colorectal cancers. , 1990, Science.

[12]  N. Rosen,et al.  Activation of pp60c-src protein kinase activity in human colon carcinoma. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[13]  O. Kronborg,et al.  Clonal karyotypic abnormalities in colorectal adenomas: Clues to the early genetic events in the adenoma‐carcinoma sequence , 1994 .

[14]  O. Kronborg,et al.  Karyotypic characterization of colorectal adenocarcinomas , 1995, Genes, chromosomes & cancer.

[15]  D. Ward,et al.  Simultaneous visualization of seven different DNA probes by in situ hybridization using combinatorial fluorescence and digital imaging microscopy. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[16]  E. Schröck,et al.  Molecular cytogenetic analysis of formalin-fixed, paraffin-embedded solid tumors by comparative genomic hybridization after universal DNA-amplification. , 1993, Human molecular genetics.

[17]  P. Brusa,et al.  Clonal chromosome aberrations in normal kidney tissue from patients with renal cell carcinoma. , 1989, Cancer genetics and cytogenetics.

[18]  P. Nowell.  The clonal evolution of tumor cell populations. , 1976, Science.

[19]  M R Speicher,et al.  Quantitative analysis of comparative genomic hybridization. , 1995, Cytometry.

[20]  J. Arends,et al.  Chromosome aberrations in adenomas of the colon. Proof of trisomy 7 in tumor cells by combined interphase cytogenetics and immunocytochemistry , 1994, International journal of cancer.

[21]  B. Dutrillaux,et al.  Cytogenetic study of 30 colorectal adenomas. , 1994, Cancer genetics and cytogenetics.

[22]  D. Pinkel,et al.  Comparative Genomic Hybridization for Molecular Cytogenetic Analysis of Solid Tumors , 2022 .

[23]  B. Vogelstein,et al.  Prevalence of ras gene mutations in human colorectal cancers , 1987, Nature.

[24]  E. Schröck,et al.  Gain of chromosome 3q defines the transition from severe dysplasia to invasive carcinoma of the uterine cervix. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[25]  B. Vogelstein,et al.  A genetic model for colorectal tumorigenesis , 1990, Cell.

[26]  A. Jauch,et al.  Correlation of microscopic phenotype with genotype in a formalin-fixed, paraffin-embedded testicular germ cell tumor with universal DNA amplification, comparative genomic hybridization, and interphase cytogenetics. , 1995, The American journal of pathology.

[27]  J. Cigudosa,et al.  Trisomy 7 in nonneoplastic kidney tissue cultured with and without epidermal growth factor. , 1992, Cancer genetics and cytogenetics.