Breast cancer genetic evolution: I. Data from cytogenetics and DNA content

Abstract

A general scheme of chromosome alterations occurring during tumor progression is proposed from the cytogenetic study of 113 breast carcinomas. For 76 of these tumors, chromosome numbers and rate of chromosome rearrangements were correlated with DNA content studied by flow cytometry. A series of 536 cases was used as control for flow cytometry. The following evolution can be proposed: 1. occurrence of unbalanced rearrangements decreasing chromosome number and DNA content; 2. correlatively to the rate of chromosome rearrangements, formation of endoreduplications leading to hyperploid sidelines; 3. persistence of the near diploid cells and decrease of chromosome number to about 35 and of DNA index to .85; 4. more frequently, elimination of the near diploid cells and complete passage to hyperploidy; 5. further losses of chromosomes in the hyperploid tumors, whose karyotypes can decrease to about 55 chromosomes and a DNA index of 1.35; 6. eventually, occurrence of a second endoreduplication, leading to an apparent near tetraploidy. The rate of rearranged chromosomes may reach 80% in both near diploid tumors with 35-40 and hyperploid tumors with 55-65 chromosomes which can be regarded as those with the highest degree of tumor progression. It is shown that the increase of chromosome number and DNA index above diploidy is very limited, and that all tumors with more than 50 chromosomes and 1.35 DNA content passed through endoreduplication. This results in many possible losses of heterozygosity in these cases.

Comparative genomic hybridisation of ductal carcinoma in situ of the breast: identification of regions of DNA amplification and deletion in common with invasive breast carcinoma

“…Indeed, abnormalities of this chromosome are also consistently observed in other cancers (Teyssier, 1989). Karyotyping of breast cancer cell lines has shown that the most frequent aberrations (Dutrillaux et al, 1990(Dutrillaux et al, , 1991. Loss of 16q was the sole abnormality detected by CGH in DCIS case 3325.…”

Chromosomal imbalances in primary and metastatic pancreatic carcinoma as detected by interphase cytogenetics: basic findings and clinical aspects

“…Solinas-Toldo et al (1996) found gain of 8q in 3 of 27 primary tumours, whereas Fukushige et al (1997) (Dutrillaux et al, 1991). Endoreduplication, accompanying tumour progression, may also turn monosomy 18 of primary carcinomas into 'relative loss' of chromosome 18, which was indeed observed in one metastatic specimen (E4; relative loss of a chromosome means under-representation in relation to the defined ploidy, whereas monosomy indicates the presence of a single copy of this chromosome).…”

Effects of hTERT on metal ion-induced genomic instability

“…This may allow damaging agents like metals to cause tetraploidy, which would not be caused in hTERTÀ cells. This mechanism could be important in carcinogenesis in which the induction of telomerase positivity and tetraploidy are early steps in malignancy (Reid et al, 1987;Dutrillaux et al, 1991;Rajagopalan and Lengauer, 2004). It is interesting that an example of transformation to a near tetraploid state has been described in tissue culture of Barrett's epithelium, which was transfected with hTERT (Corinna et al, 2003).…”