Cytogenetic study in a mentally retarded child with bloom syndrome and acute lymphoblastic leukemia

Werner‐Favre, Christiane; Wyss, M; Cabrol, C; Félix, Françoise; Guenin, Rita; Laufer, Daniel; Engel, Eric

doi:10.1002/ajmg.1320180205

Cited by 10 publications

(3 citation statements)

References 13 publications

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“…BLM may play a role in early S phase-speci®c DNA surveillance mechanisms resulting in the disruption of recombinogenic molecules that arise at sites of stalled replication forks and guidance of the above-mentioned large repair complex to a damaged base on a DNA strand. Chromosomal quadriradials are well described as one of the representative phenotypes seen in BS cells (Werner-Favre et al, 1984). DNA crosslinking within GC-rich region in mammalian chromosomes can create quadriradials (Matsumoto et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Bloom helicase is involved in DNA surveillance in early S phase in vertebrate cells

et al. 2001

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Section: Discussionmentioning

confidence: 99%

Bloom helicase is involved in DNA surveillance in early S phase in vertebrate cells

et al. 2001

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“…Chromosomal aberrations including translocations have also been described in BS patients (4,39,71,85,102). Furthermore, the repeated observation of partial or complete loss of chromosome 7 in bone marrow cells of BS patients with acute lymphoblastic or myeloblastic leukemia may indeed suggest that lack of BLM can increase the frequency of specific, recurring chromosomal rearrangements (4,39,71,85).…”

Section: Figmentioning

confidence: 99%

Control of Translocations between Highly Diverged Genes by Sgs1, the Saccharomyces cerevisiae Homolog of the Bloom'sSyndrome Protein

Schmidt

Kolodner

2006

Molecular and Cellular Biology

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Sgs1 is a RecQ family DNA helicase required for genome stability in Saccharomyces cerevisiae whose human homologs BLM, WRN, and RECQL4 are mutated in Bloom's, Werner, and Rothmund Thomson syndromes, respectively. Sgs1 and mismatch repair (MMR) are inhibitors of recombination between similar but divergent (homeologous) DNA sequences. Here we show that SGS1, but not MMR, is critical for suppressing spontaneous, recurring translocations between diverged genes in cells with mutations in the genes encoding the checkpoint proteins Mec3, Rad24, Rad9, or Rfc5, the chromatin assembly factors Cac1 or Asf1, and the DNA helicase Rrm3. The S-phase checkpoint kinase and telomere maintenance factor Tel1, a homolog of the human ataxia telangiectasia (ATM) protein, prevents these translocations, whereas the checkpoint kinase Mec1, a homolog of the human ATM-related protein, and the Rad53 checkpoint kinase are not required. The translocation structures observed suggest involvement of a dicentric intermediate and break-induced replication with multiple cycles of DNA template switching.RecQ-like DNA helicases play important roles in the maintenance of genome stability from bacteria to humans. The only member of the RecQ family of 3Ј to 5Ј DNA helicases in the yeast Saccharomyces cerevisiae is Sgs1. Sgs1 has been implicated in the coordination between DNA replication and recombination, in the regulation of homologous recombination (HR) and the suppression of crossover products during HR, and in S-phase checkpoint activation as well as in transcription (16,26,38,49,61,96). As a consequence, cells that lack Sgs1 display a hyperrecombination phenotype, accumulate extrachromosomal ribosomal DNA (rDNA) circles, frequently missegregate chromosomes during mitosis and meiosis, have modestly increased rates of accumulating gross chromosomal rearrangements (GCRs), are sensitive to agents such as hydroxyurea and methyl-methanesulfonate, and show signs of premature aging (29,58,61,86,100,101,104).To date, five human genes encoding RecQ-like (RECQL) proteins have been identified. Mutations in RECQL2 (WRN) (105), RECQL3 (BLM) (23), and RECQL4 (41, 42) cause three rare, cancer-prone disorders, Werner syndrome (WS), Bloom's syndrome (BS), and a subset of Rothmund Thomson syndrome (Type II RTS) (97), respectively, while defects in RECQL1 (73, 74) and RECQL5 (41) have not been linked to a disease. Besides short stature, early onset of diabetes mellitus, and immunodeficiency, BS is characterized by extreme cancer risk, which has been estimated to be 150 to 300 times higher than the risk of malignancy in the unaffected population; in 168 BS patients, 100 cancers of many types had arisen at a mean age of 24.7 years, with many of the patients suffering from multiple primary cancers (31). Although WS patients share some of these symptoms, including early onset of diabetes mellitus and increased cancer susceptibility, they also show numerous other signs of accelerated aging not typical for BS. RTS patients also show a high prevalence of cancers, especially...

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“…More than half of the BS patients reported to the BS registry (http://weill.cornell.edu/bsr/genetics/) have developed cancer, 10-15% of which are haematological. In children several communications have described acute lymphoblastic leukemia (ALL) (4), myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) (5, 6), as has been in adults (7). Here we report the clinical findings and course of a girl with BS due to compound heterozygosity for a novel and a previously described BLM mutation, who developed ALL and secondary AML with a short latency, and discuss clinical and genetic implications.…”

Section: Introductionmentioning

confidence: 99%

Acute Myeloid Leukaemia after Treatment for Acute Lymphoblastic Leukaemia in Girl with Bloom Syndrome

Adams¹,

Jenney²,

Lazarou

et al. 2013

J Genet Syndr Gene Ther

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Bloom syndrome (BS) is an inherited genomic instability disorder caused by disruption of the BLM helicase and confers an extreme cancer predisposition. Here we report on a girl with BS who developed acute lymphoblastic leukaemia (ALL) at age nine, and treatment-related acute myeloid leukaemia (t-AML) aged 12. She was compound heterozygous for the novel BLM frameshift deletion c.1624delG and the previously described c.3415C>T nonsense mutation. Two haematological malignancies in a child with BS imply a fundamental role for BLM for normal haematopoiesis, in particular in the presence of genotoxic stress.

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Cytogenetic study in a mentally retarded child with bloom syndrome and acute lymphoblastic leukemia

Cited by 10 publications

References 13 publications

Bloom helicase is involved in DNA surveillance in early S phase in vertebrate cells

Bloom helicase is involved in DNA surveillance in early S phase in vertebrate cells

Control of Translocations between Highly Diverged Genes by Sgs1, the Saccharomyces cerevisiae Homolog of the Bloom'sSyndrome Protein

Acute Myeloid Leukaemia after Treatment for Acute Lymphoblastic Leukaemia in Girl with Bloom Syndrome

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