CTG triplet repeat expansion in a laryngeal carcinoma from a patient with myotonic dystrophy

Osanai, Ryuichi; Kinoshita, M.; Hirose, Kazuhiko; Homma, Teiichi; Kawabata, Isuzu

doi:10.1002/(sici)1097-4598(200005)23:5<804::aid-mus19>3.0.co;2-e

Cited by 22 publications

(14 citation statements)

References 22 publications

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“…In our sub-analysis, however, we did not observe an association between leukocyte DNA repeat expansion size and tumor development in either DM1 or DM2 patients. Past studies of neoplasms from DM1 patients have found that tumors contained longer CTG-repeat expansions than adjacent normal tissue [22–24]. The high degree of tissue mosaicism in DM1 patients may provide an explanation as to why the repeat expansion size measured in peripheral blood DNA is not associated with tumor development in DM patients [25, 26].…”

Section: Discussionmentioning

confidence: 99%

Correlates of tumor development in patients with myotonic dystrophy

et al. 2012

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Patients with myotonic dystrophy (DM) have recently been reported to be at increased risk of tumor development, but clinical associations related to this observation are unknown. We calculated the odds ratios (ORs) and 95% confidence intervals (CI) of self-reported tumor development by patients’ demographic and clinical characteristics to evaluate factors associated with tumor development in DM patients, using data from the National Registry of Myotonic Dystrophy and Facioscapulohumeral Dystrophy Patients and Family Members. Of the 911 participants, 47.5% were male and 85.7% had DM type 1 (DM1). Compared with DM1, patients with DM type 2 (DM2) were older at Registry enrollment (median age =55 vs. 44 years, p<0.0001) and at DM diagnosis (median age= 48 vs. 30 years, p<0.0001); and more likely to be females (p=0.001). At enrollment, 95 (10.4%) DM patients reported a history of benign or malignant tumor. Tumors were associated with female gender (OR=1.9, 95% CI=1.2–3.1, p=0.007) and DM1 (OR=2.1, 95% CI=1.1–4.1, p=0.03). In a subgroup analysis of patients with blood-based DNA testing results (397 DM1, 54 DM2), repeat expansion size was not associated with tumor risk in DM1 (p=0.26) or DM2 (p=0.34). In conclusion, female gender and DM1 subtype, but not DNA repeat expansion size, were associated with increased risk of tumors in DM. Follow-up studies are warranted to determine if oncogenes associated with dystrophia myotonica-protein kinase (DMPK) are altered in DM, and to determine if repeat expansion size, as in our study, is not associated with tumor development.

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Section: Discussionmentioning

confidence: 99%

Correlates of tumor development in patients with myotonic dystrophy

et al. 2012

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“…Interestingly, in the limited number of instances in which DM1-related neoplasms have been studied, the tumors contained repeat expansions that were considerably longer than those assayed in non-neoplastic tissue from the same organ, or from the patient’s skeletal muscle and/or leukocytes [3–7]. It is uncertain whether this repeat expansion was secondary to tumorigenesis-related cell proliferation, or whether the somatic instability of repeat length seen commonly in DM, with repeat size increasing with age and at different rates in various tissues, leads to a critical threshold of sequestration of RNA binding proteins, possibly resulting in the upregulation of Wnt /β- catenin signaling in a tissue specific manner.…”

Section: Hypothesis: Tumorigenesis In Dmmentioning

confidence: 99%

“…In reflecting on our clinical experience caring for large numbers of DM patients, we have questioned whether there might be an increased incidence of other tumors in patients with DM. Furthermore, in the limited number of tumors that have been studied in DM patients, increased trinucleotide repeat expansion in the DM1 has been demonstrated, suggesting that somehow this underlying genetic instability may predispose these patients to developing tumors; no DM2 tumors have been studied [3–7]. …”

Section: Introductionmentioning

confidence: 99%

Hypothesis: neoplasms in myotonic dystrophy

Mueller

Hilbert

Martens

et al. 2009

Cancer Causes Control

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Tumorigenesis is a multi-step process due to an accumulation of genetic mutations in multiple genes in diverse pathways which ultimately lead to loss of control over cell growth. It is well known that inheritance of rare germline mutations in genes involved in tumorigenesis pathways confer high lifetime risk of neoplasia in affected individuals. Furthermore, a substantial number of multiple malformation syndromes include cancer susceptibility in their phenotype. Studies of the mechanisms underlying these inherited syndromes have added to the understanding of both normal development and the pathophysiology of carcinogenesis. Myotonic dystrophy (DM) represents a group of autosomal dominant, multisystemic diseases that share the clinical features of myotonia, muscle weakness, and early-onset cataracts. Myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) result from unstable nucleotide repeat expansions in their respective genes. There have been multiple reports of tumors in individuals with DM, most commonly benign calcifying cutaneous tumors known as pilomatricomas. We provide a summary of the tumors reported in DM and a hypothesis for a possible mechanism of tumorigenesis. We hope to stimulate further study into the potential role of DM genes in tumorigenesis, and help define DM pathogenesis, and facilitate developing novel treatment modalities.

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“…In this case, the patient demonstrated the classic clinical and electrophysiological features of DM1, but electrodiagnostic findings were only consistent with MG. In addition to thymomas, other neoplasms, both benign and malignant, have been identified in patients with DM1, including dermatologic tumors such as basal cell carcinomas1 and pilomatrixomas,8 insulinomas,14, 33 laryngeal carcinomas,24 renal cell carcinomas, neural crest–derived tumors,13 parathyroid adenomas,13 ovarian carcinoma,17 adenocarcinomas of the colon14 and small intestine,13 and gastric adenocarcinomas 14. Whether the occurrence of these tumors in DM1 is mere coincidence or a true association with the muscle disease remains to be proven, and more investigation is clearly needed.…”

Section: Discussionmentioning

confidence: 99%

Myotonic dystrophy type 1 coexisting with myasthenia gravis and thymoma

2008

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Myotonic dystrophy type 1 (DM1) is an autosomal-dominant multisystemic disorder that may rarely be associated with benign and malignant neoplasms. Cases of both thymoma and myasthenia gravis in association with DM1 are extremely rare. A literature review revealed only three prior reports. We present a 51-year-old man with a family history of DM1 and fluctuating diplopia and ptosis, who was found to have acetylcholine receptor-binding antibodies, thymoma, and a clinical presentation compatible with ocular myasthenia gravis as well as positive genetic testing for DM1. Needle electromyographic (EMG) study demonstrated diffuse runs of myotonic discharges in multiple muscles, consistent with the diagnosis of DM1. Single-fiber EMG showed both increased jitter and blocking. Due to somatic instability, which has been shown previously in DM1, the myotonin protein kinase (DMPK) gene appears to act as a tumor suppressor. Therefore, abnormal CTG repeat expansions in the gene could lead to the development of thymoma and myasthenia gravis.

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CTG triplet repeat expansion in a laryngeal carcinoma from a patient with myotonic dystrophy

Cited by 22 publications

References 22 publications

Correlates of tumor development in patients with myotonic dystrophy

Correlates of tumor development in patients with myotonic dystrophy

Hypothesis: neoplasms in myotonic dystrophy

Myotonic dystrophy type 1 coexisting with myasthenia gravis and thymoma

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