Rothmund-Thomson syndrome with osteosarcoma

Drouin, Christian A.; Mongrain, Éric; Sasseville, Denis; Bouchard, H; Drouin, M.

doi:10.1016/0190-9622(93)70040-z

Cited by 45 publications

(21 citation statements)

References 25 publications

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“…In contrast to previous studies, we report a male preponderance (M:F 2:1), a low prevalence of cataracts (7%), a high prevalence of OS (32%), and gastrointestinal problems (17%). The male preponderance contrasts with earlier claims of either female predominance [Drouin et al, 1993;Spurney et al, 1998] or equal M:F ratio [Vennos et al, 1992]. Our ascertainment should not be biased for Fig.…”

Section: Discussioncontrasting

confidence: 69%

Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients

et al. 2001

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Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive genodermatosis characterized by a poikilodermatous rash starting in infancy, small stature, skeletal abnormalities, juvenile cataracts, and predisposition to specific cancers. We have identified a contemporary cohort of 41 patients to better define the clinical profile, diagnostic criteria, and management of patients with RTS. Patients with the diagnosis of RTS were ascertained by referrals from dermatology, ophthalmology, genetics, and oncology or from direct contact with the patient's family. Medical information was obtained from interviews with physicians, patients, and their parents and a review of medical records. The age range at ascertainment was 9 months to 42 years (28 males and 13 females; M:F, 2:1). All subjects displayed a characteristic rash. Thirteen subjects had osteosarcoma (OS) (32%), eight had radial defects (20%), seven had gastrointestinal findings (17%), two had cataracts (6%), and one had skin cancer (2%). Twenty-two of 28 patients without OS were less than 15 years old and thus remain at significant risk for this tumor. This case-series study reveals a clinical profile of RTS that includes a higher prevalence of OS and fewer cataracts, compared with historical reports. These differences may reflect either allelic or genetic heterogeneity. This study documents the frequency of clinical anomalies in a contemporary cohort of RTS patients and revises guidelines for diagnosis and management of RTS.

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Section: Discussioncontrasting

confidence: 69%

Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients

et al. 2001

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“…anaemia, dyskeratosis congenita, Bloom's synOn reviewing the previously published cases of drome, ataxia-telangiectasia), a DNA repair defect osteosarcomas associated with RTS, we did not has been searched for in RTS. It is now recognized find the male predominance described by Drouin that the fibroblasts of patients with RTS have a et al [ 3] who observed a male5female ratio of 651 diminished capacity of DNA-repair following which contrasted with the female predominance lesions induced by an exposure to oncogenic stimreported in RTS alone [6,8,9]. uli such as gamma radiation.…”

Section: Case Reportmentioning

confidence: 99%

“…The prognosis is very poor with a mean life expectancy of 1 year. To our knowledge, 11 cases of osteosarcoma have already been reported in RTS [1][2][3][4][5][6][7][8][9][10][11]. Whether osteosarcomatosis is truly a multifocal osteosarcoma or is a rapidly metastasizing unifocal osteosarcoma, it remains a rare entity that has been described only once previously in association with RTS [ 8].…”

mentioning

confidence: 99%

Osteosarcomatosis with Rothmund-Thomson syndrome.

El-Khoury

Haddad²,

Atallah³

1997

The British Journal of Radiology

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We describe the second reported case of multicentric osteosarcoma associated with Rothmund-Thomson syndrome (RTS), a rare hereditary cancer-prone genodermatosis characterized by typical cutaneous lesions and other non-dermatological pathological manifestations, particularly skeletal changes. A high incidence of malignant disorders has been found in RTS patients. This could be explained by the diminished capacity of DNA-repair demonstrated in the fibroblasts of RTS patients following exposure to oncogenic stimuli. The severe cutaneous lesions and the benign bone lesions found in RTS may be considered a predisposing factor to the particularly frequent skin carcinoma and osteogenic sarcoma encountered in these cancer-prone patients. A brief review of the literature is given, with a discussion of the association between these two rare conditions.

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“…RECQ4 has been shown to be part of a stable complex in the cytoplasm with the ubiquitin ligases, UBR1 and UBR2 (Yin et al, 2004). The pathological association between a subset of RTS patients and osteosarcoma has long been observed (Drouin et al, 1993;el-Khoury et al, 1997). The molecular basis of this is probably due to the mutations in the RECQ4 gene.…”

Section: Introductionmentioning

confidence: 99%

Tumor suppressor p53 represses transcription of RECQ4 helicase

et al. 2005

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RECQ4 is a member of the RecQ helicase family, which has been implicated in the regulation of DNA replication, recombination and repair. p53 modulates the functions of RecQ helicases including BLM and WRN. In this study, we demonstrate that p53 can regulate the transcription of RECQ4. Using nontransformed, immortalized normal human fibroblasts, we show that p53-dependent downregulation of RECQ4 expression occurred in G1-arrested cells, both in the absence or presence of exogenous DNA damage. Wild-type p53 (but not the tumor-derived mutant forms) repressed RECQ4 promoter activity. The camptothecin or etoposide-dependent p53-mediated repression was attenuated by trichostatin A (TSA), an inhibitor of histone deacetylases (HDACs). Repression of the RECQ4 promoter was accompanied with an increased accumulation of HDAC1, and the loss of SP1 and p53 binding to the promoter. The simultaneous formation of a camptothecin-dependent p53-SP1 complex indicated its occurrence outside of the RECQ4 promoter. These data suggest that p53-mediated repression of RECQ4 transcription during DNA damage results from the modulation of the promoter occupancy of transcription activators and repressors.

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Rothmund-Thomson syndrome with osteosarcoma

Cited by 45 publications

References 25 publications

Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients

Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients

Osteosarcomatosis with Rothmund-Thomson syndrome.

Tumor suppressor p53 represses transcription of RECQ4 helicase

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