Chromosome abnormalities in 10 lung cancer cell lines of the NCI-H series analyzed with spectral karyotyping

Grigorova, M.; Lyman, Rachel C.; Caldas, Carlos; Edwards, Paul A.W.

doi:10.1016/j.cancergencyto.2005.03.007

Cited by 33 publications

(31 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, dysregulated recombination causing genomic restructuring of centromeric α-satellite repeats may result in centromeric dysfunction, contributing to the aneuploidy commonly seen in adult solid tumors (21). Intriguingly, other highly self-similar clustered gene loci in the human genome (22) express protein products found with relative specificity only in cancer and in highly recombination-active tissues such as testis: the so-called "CT" genes (23).…”

Section: Discussionmentioning

confidence: 99%

Human rRNA Gene Clusters Are Recombinational Hotspots in Cancer

et al. 2009

View full text Add to dashboard Cite

The gene that produces the precursor RNA transcript to the three largest structural rRNA molecules (rDNA) is present in multiple copies and organized into gene clusters. The 10 human rDNA clusters represent <0.5% of the diploid human genome but are critically important for cellular viability. Individual genes within rDNA clusters possess very high levels of sequence identity with respect to each other and are present in high local concentration, making them ideal substrates for genomic rearrangement driven by dysregulated homologous recombination. We recently developed a sensitive physical assay capable of detecting recombination-mediated genomic restructuring in the rDNA by monitoring changes in lengths of the individual clusters. To prove that this dysregulated recombination is a potential driving force of genomic instability in human cancer, we assayed the rDNA for structural rearrangements in prospectively recruited adult patients with either lung or colorectal cancer, and pediatric patients with leukemia. We find that over half of the adult solid tumors show detectable rDNA rearrangements relative to either surrounding nontumor tissue or normal peripheral blood. In contrast, we find a greatly reduced frequency of rDNA alterations in pediatric leukemia. This finding makes rDNA restructuring one of the most common chromosomal alterations in adult solid tumors, illustrates the dynamic plasticity of the human genome, and may prove to have either prognostic or predictive value in disease progression. [Cancer Res 2009;69(23):9096-104]

show abstract

Section: Discussionmentioning

confidence: 99%

Human rRNA Gene Clusters Are Recombinational Hotspots in Cancer

et al. 2009

View full text Add to dashboard Cite

show abstract

“…The spectral karyotype of NCI-H1770 was pseudotetraploid and showed a large HSR of chromosome 2 origin inserted into chromosome 12 (Grigorova et al 2005) (Supplemental Fig. 2).…”

Section: Spectral Karyotype and Fish Analysismentioning

confidence: 99%

Architectures of somatic genomic rearrangement in human cancer amplicons at sequence-level resolution

Bignell¹,

Santarius²,

Pole³

et al. 2007

Genome Res.

Self Cite

188

177

View full text Add to dashboard Cite

For decades, cytogenetic studies have demonstrated that somatically acquired structural rearrangements of the genome are a common feature of most classes of human cancer. However, the characteristics of these rearrangements at sequence-level resolution have thus far been subject to very limited description. One process that is dependent upon somatic genome rearrangement is gene amplification, a mechanism often exploited by cancer cells to increase copy number and hence expression of dominantly acting cancer genes. The mechanisms underlying gene amplification are complex but must involve chromosome breakage and rejoining. We sequenced 133 different genomic rearrangements identified within four cancer amplicons involving the frequently amplified cancer genes MYC, MYCN, and ERBB2. The observed architectures of rearrangement were diverse and highly distinctive, with evidence for sister chromatid breakage-fusion-bridge cycles, formation and reinsertion of double minutes, and the presence of bizarre clusters of small genomic fragments. There were characteristic features of sequences at the breakage-fusion junctions, indicating roles for nonhomologous end joining and homologous recombination-mediated repair mechanisms together with nontemplated DNA synthesis. Evidence was also found for sequence-dependent variation in susceptibility of the genome to somatic rearrangement. The results therefore provide insights into the DNA breakage and repair processes operative in somatic genome rearrangement and illustrate how the evolutionary histories of individual cancers can be reconstructed from large-scale cancer genome sequencing.

show abstract

“…The alteration was observed in all the seven cell lines, therefore, was indicated to be a common alteration causing LOH. A recent SKY analysis of lung cancer cell lines revealed that translocations are present in all 10 cases examined and the great majority (>90%) of the translocations were unbalanced ones (Grigorova et al, 2005). In fact, all the seven cell lines examined in the present study carried translocations (4-15 transloca- tions), and 114 translocations in total were detected in these cases.…”

Section: Discussionmentioning

confidence: 71%

Unbalanced translocation, a major chromosome alteration causing loss of heterozygosity in human lung cancer

Ogiwara¹,

Nakanishi²,

Nagayama³

et al. 2008

Oncogene

View full text Add to dashboard Cite

Loss of heterozygosity (LOH) is a major genetic event causing inactivation of tumor suppressor genes in human carcinogenesis. To elucidate chromosomal mechanisms causing LOH, 201 LOHs in 10 cases of human lung cancer, which were detected by a genome-wide single nucleotide polymorphism array analysis, were investigated for responsible chromosome alterations by integrating information on breakpoints for DNA copy number changes obtained by array-comparative genome hybridization and on numerical and structural chromosomal alterations obtained by spectral karyotyping. The majority (80%) of LOHs were partial chromosome LOHs caused by structural chromosomal alterations, while the remaining (20%) were whole chromosome LOHs caused by whole chromosome deletions. Unbalanced translocation was defined as the most frequent alteration, and it accounted for 30% of all LOHs. Three other structural alterations-interstitial deletion (19%), mitotic recombination (9%) and gene conversion (6%)-also contributed to the occurrence of LOH, while terminal deletion contributed to only a small subset (1%). Since unbalanced translocation is a common chromosomal alteration in lung cancer cells, the results in the present study strongly indicate that a considerable fraction of LOHs detected in lung cancer cells are caused by unbalanced translocation.

show abstract

Chromosome abnormalities in 10 lung cancer cell lines of the NCI-H series analyzed with spectral karyotyping

Cited by 33 publications

References 32 publications

Human rRNA Gene Clusters Are Recombinational Hotspots in Cancer

Human rRNA Gene Clusters Are Recombinational Hotspots in Cancer

Architectures of somatic genomic rearrangement in human cancer amplicons at sequence-level resolution

Unbalanced translocation, a major chromosome alteration causing loss of heterozygosity in human lung cancer

Contact Info

Product

Resources

About