Chromosome analysis of 97 primary breast carcinomas: Identification of eight karyotypic subgroups

Abstract

Chromosome banding analysis of 97 short-term cultured primary breast carcinomas revealed clonal aberrations in 79 tumors, whereas 18 were karyotypically normal. In 34 of the 79 tumors with abnormalities, two to eight clones per case were detected; unrelated clones were present in 27 (34%) cases, whereas only related clones were found in seven. These findings indicate that a substantial proportion of breast carcinomas are of polyclonal origin. Altogether eight abnormalities were repeatedly identified both as sole chromosomal anomalies and as part of more complex karyotypes: the structural rearrangements i(1)(q10), der(1:16)(q10;p10), del(1)(q11-12), del(3)(p12-13p14-21), and del(6)(q21-22) and the numerical aberrations +7, +18, and +20. At least one of these changes was found in 41 (52%) of the karyotypically abnormal tumors. They identify a minimum number of cytogenetic subgroups in breast cancer and are likely to represent primary chromosome anomalies in this type of neoplasia. Other candidates for such a role are translocations of 3p12-13 and 4q21 with various partner chromosomes and inversions of chromosome 7, which also were seen repeatedly. Additional chromosomal aberrations that give the impression of occurring nonrandomly in breast carcinomas include structural rearrangements leading to partial monosomies for 1p, 8p, 11p, 11q, 15p, 17p, 19p, and 19q and losses of one copy of chromosomes X, 8, 9, 13, 14, 17, and 22. The latter changes were seen consistently only in complex karyotypes, however, and we therefore interpret them as being secondary anomalies acquired during clonal evolution.

Simultaneous chromosome 1q gain and 16q loss is associated with steroid receptor presence and low proliferation in breast carcinoma

“…12 A labeling index was obtained for all the biologic parameters evaluated by image cytometry and expressed as the percentage of the labeled nuclear area over the total neoplastic nuclear area (percentage Labeling Index area, %LIa). All the above-mentioned parameters were categorized using the following cutoff values: ER and PR %LIa o10% ¼ negative, Z10% positive; cyclin D1 %LIa o5% ¼ negative, Z5% ¼ positive; CycA %LIa o20% ¼ negative, Z20% ¼ positive; p21 %LIa o10% ¼ negative; Z10% ¼ positive; p27 %LIa o50% ¼ negative, Z50% ¼ positive; p53 %LIa o 4% ¼ negative (1), Z4% and o30% ¼ intermediate (2), Z30% ¼ positive (3); pRB loss of expression was recorded as previously detailed 13 and reported using two categories: 0 ¼ loss of function, 1 ¼ functional pRB protein; Ki-67 %LIa o20% ¼ low proliferation (1) and Z20% ¼ high proliferation (2).…”

“…Chromosome 1q gains and 16q losses have often been described to be simultaneously present in breast carcinoma samples by karyotype analysis 1,2 and comparative genomic hybridization (CGH) studies. 3,4 Gains of the long arm of chromosome 1 and losses of chromosome 16q are often the result of unbalanced translocations between these two chromosomes: 1,6 less frequently, they are the result of other rearrangements.…”

“…3,4 Gains of the long arm of chromosome 1 and losses of chromosome 16q are often the result of unbalanced translocations between these two chromosomes: 1,6 less frequently, they are the result of other rearrangements. 2,5 Chromosome 1q gains and 16q losses are considered as early changes since they have been detected as the sole chromosome abnormalities in near-diploid breast carcinoma 1,6 and in well-differentiated samples with a few alterations. 3,7 These genetic changes and the resulting chromosome imbalances have been thought to play a pathogenic role in breast carcinoma development.…”

Multicolour-banding fluorescence in situ hybridisation (mbanding-FISH) to identify recurrent chromosomal alterations in breast tumour cell lines

“…This chromosome is one of the most frequently affected in breast cancers (Dutrillaux et al, 1990;Bièche et al, 1993;Pandis et al, 1995;Teixeira et al, 2002; http://cgap.nci.nih.gov/Chromosomes/ RecurrentAberrations). Analyses of breast tumours have established a frequency of breaks as follows: 1p36 (6.5%), 1p22 (6.1%), 1p13 (5.9%), 1q10 (24%), 1q11 -12 (7%), 1q21 (9.1%), 1q25 (5%) and 1q42 (5.9%) (Teixeira et al, 2002).…”

Pattern of Chromosome 16q Loss Differs between an Atypical Proliferative Lesion and an Intraductal or Invasive Ductal Carcinoma Occurring Subsequently in the Same Area of the Breast

“…However, recent studies have disclosed that the statuses of chromosome 16 markedly differ between the group comprising noncomedo DCIS and low-to intermediate-grade invasive carcinomas and another group comprising comedo DCIS and high-grade invasive carcinomas. In the former group, LOH on 16q is mostly accompanied by the surplus 1q arm(s) and clonal fusion(s) between the 1q and the residual fragment of chromosome 16, which generates a translocation der(16)t(1;16) (25)(26)(27).…”