Are robertsonian translocations rare in cancers?

Multani, Asha S.; Kacker, R. K.; Pathak, Sen

doi:10.1016/s0165-4608(96)00182-3

Cited by 4 publications

(2 citation statements)

References 19 publications

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“…These cells were treated with 10 mg colcemide for 4 h and stained with a subtelomere probe (green), a MSR probe in the Table S1 for absolute numbers and summary of statistical analysis). RbTs are chromosome rearrangements that involve the centric fusion of two acrocentric chromosomes to form a single metacentric chromosome (36) and are known to increase cancer risk (37), spontaneous abortions (38), and male infertility (39). These RbTs do not contain telomeres at the fusion site as observed by two-color FISH (only DAPI and the telomere probe were used; Fig.…”

Section: Resultsmentioning

confidence: 99%

Cisplatin Depletes TREX2 and Causes Robertsonian Translocations as Seen in TREX2 Knockout Cells

et al. 2007

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Cisplatin, an anticancer drug, forms DNA interstrand crosslinks (ICL) that interfere with replication, whereas TREX2 is a 3 ¶!5 ¶ exonuclease that removes 3 ¶ mismatched nucleotides and promotes cellular proliferation. Here, we show that TREX2 is depleted in human cells derived from cancer after exposure to cisplatin but not other genotoxins including another cross-linking agent, mitomycin C (MMC), indicating a potential role for TREX2 depletion in cisplatin-induced cytotoxicity. To better understand TREX2 cellular function, we deleted TREX2 in mouse embryonic stem (ES) cells by gene targeting and find these cells exhibit reduced proliferation and gross chromosomal rearrangements including Robertsonian translocations (RbT). Quite interestingly, ES cells exposed to cisplatin also exhibit RbTs. By contrast, RbTs are not observed for ES cells exposed to MMC, indicating that RbTs are not caused by ICLs but instead TREX2 depletion by either cisplatin exposure or mutation. Taken together, our results show that cisplatin depletes TREX2 and causes genomic instability that is similarly observed in TREX2-mutant cells. Thus, cisplatin has two potential cytotoxic activities: (a) the generation of ICLs and (b) the depletion of

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Section: Resultsmentioning

confidence: 99%

Cisplatin Depletes TREX2 and Causes Robertsonian Translocations as Seen in TREX2 Knockout Cells

et al. 2007

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“…RbTs are chromosome rearrangements involving centric fusion of two acrocentric chromosomes to form a single metacentric chromosome that results from deletion of the p arms from both chromosomes [13,14]. RbTs may influence speciation [15,16] and may increase cancer risk [17], spontaneous abortions [18] and male infertility [19]. Thus, Trex2 maintains chromosomal integrity but we do not know if the exonuclease and DNA binding activities are important for suppressing RbTs.…”

Section: Introductionmentioning

confidence: 99%

TREX2 exonuclease defective cells exhibit double-strand breaks and chromosomal fragments but not Robertsonian translocations

Dumitrache

Hasty

2009

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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TREX2 is a 3′→5′ exonuclease that binds to DNA and removes 3′ mismatched nucleotides. By an in vitro structure function analysis, we found a single amino acid change (H188A) completely ablates exonuclease activity and impairs DNA binding by about 60% while another change (R167A) impairs DNA binding by about 85% without impacting exonuclease activity. For a biological analysis, we generated trex2 null cells by deleting the entire Trex2 coding sequences in mouse embryonic stem (ES) cells. We found Trex2 deletion caused high levels of Robertsonian translocations (RbTs) showing Trex2 is important for chromosomal maintenance. Here we evaluate the exonuclease and DNA binding domains by expressing in trex2 null cells coding sequences for wild type human TREX2 (Trex2 hTX2 ) or human TREX2 with the H188A change (Trex2 H188A ) or the R167A change (Trex2 R167A ). These cDNAs are positioned adjacent to the mouse Trex2 promoter by Cre-mediated knock-in. By observing metaphase spreads, we found Trex2 H188A cells exhibited high levels of double-strand breaks (DSBs) and chromosomal fragments. Therefore, TREX2 may suppress spontaneous DSBs or exonuclease defective TREX2 may induce them in a dominate-negative manner. We also found Trex2 hTX2 , hTrex2 H188A and hTrex2 R167A cells did not exhibit RbTs. Thus, neither the exonuclease nor DNA binding domains suppress RbTs suggesting TREX2 possesses additional biochemical activities.

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Acquired Robertsonian translocations are not rare events in acute leukemia and lymphoma

Welborn

2004

Cancer Genetics and Cytogenetics

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Are robertsonian translocations rare in cancers?

Cited by 4 publications

References 19 publications

Cisplatin Depletes TREX2 and Causes Robertsonian Translocations as Seen in TREX2 Knockout Cells

Cisplatin Depletes TREX2 and Causes Robertsonian Translocations as Seen in TREX2 Knockout Cells

TREX2 exonuclease defective cells exhibit double-strand breaks and chromosomal fragments but not Robertsonian translocations

Acquired Robertsonian translocations are not rare events in acute leukemia and lymphoma

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