Differences in CTG triplet repeat expansion in leukemic cells and normal lymphocytes from a 14‐year‐old female with congenital myotonic dystrophy

Akiyama, Masaharu; Yuza, Yuki; Yokokawa, Yuichi; Yokoi, Kentaro; Ariga, Masamichi; Eto, Yoshikatsu

doi:10.1002/pbc.21654

Cited by 5 publications

(8 citation statements)

References 18 publications

(23 reference statements)

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“…Several reports have identified longer repeat expansions in tumoral cells than in nontumoral cells of DM patients; these larger expansions were thought to occur during cellular proliferation of tumoral cells. 30,31 We did not find a significant association between the presence of cancer and the number of CTG repeats in the DM1 patients with known length of CTG repeats.…”

Section: Discussioncontrasting

confidence: 58%

“… 16,18–26 The molecular mechanism of this DM‐associated carcinogenesis, however, remains uncertain; upregulation of the Wnt/β‐catenin pathway and/or alterations of the mRNAs encoding tumor suppressor genes or oncogenes have been proposed as possible etiologies 27–29 . It is unclear whether the length of the pathogenic expansion is associated with cancer risk in DM 30–32 …”

Section: Introductionmentioning

confidence: 99%

“…[27][28][29] It is unclear whether the length of the pathogenic expansion is associated with cancer risk in DM. [30][31][32] The 2018 consensus-based care recommendations for adults with DM1 call for screening for pilomatricomas (hair matrix cells-derived benign calcifying skin tumors), following the cancer screening guidelines for the general population, and considering cancer investigations in the presence of suspicious organ-related symptoms. 33 In 2019, similar recommendations for DM2 patients were published, excluding those related to the detection of pilomatricomas, which are not associated with this disease form.…”

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confidence: 99%

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Frequency and type of cancers in myotonic dystrophy: A retrospective cross‐sectional study

et al. 2023

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Introduction/Aims Myotonic dystrophies (DMs) are autosomal dominant diseases in which expression of a mutant expanded repeat mRNA leads to abnormal splicing of downstream effector genes thought to be responsible for their multisystem involvement. Cancer risk and cancer‐related deaths are increased in DM patients relative to the general population. We aimed at determining the frequency and type of cancers in both DM1 and DM2 vs a non‐DM muscular dystrophy cohort. Methods A retrospective, cross‐sectional study was carried out on patients with genetically confirmed DM1, DM2, facioscapulohumeral muscular dystrophy (FSHD), and oculopharyngeal muscular dystrophy (OPMD) at our institutions from 2000 to 2020. Results One hundred eighty‐five DM1, 67 DM2, 187 FSHD, and 109 OPMD patients were included. Relative to non‐DM, DM patients had an increased cancer risk that was independent of age and sex. Specifically, an increased risk of sex‐related (ovarian) and non–sex‐related (non‐melanoma skin, urological, and hematological) cancers was observed in DM1 and DM2, respectively. The length of CTG repeat expansion was not associated with cancer occurrence in the DM1 group. Discussion In addition to current consensus‐based care recommendations, our findings prompt consideration of screening for skin, urological, and hematological cancers in DM2 patients, and screening of ovarian malignancies in DM1 female patients.

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Section: Discussioncontrasting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Frequency and type of cancers in myotonic dystrophy: A retrospective cross‐sectional study

et al. 2023

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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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“…It is possible that repeat expansion size may be a key de-terminant of cancer risk in this context, because nucleotide repeat expansions are longer in MMD patients compared with Huntington disease or fragile X patients, 32 and case reports have demonstrated longer nucleotide repeat expansion in tumor tissue from MMD patients compared with their normal tissue. 33,34 If proven true, we would expect that patients with type 2 MMD, who are known to have the longest repeat sizes, would have higher risk of cancer, a hypothesis that needs further investigation. The observed cancer risk differences between various repeat disorders might also be related to the precise repeat expansion location within the affected gene.…”

Section: Commentmentioning

confidence: 99%

Cancer Risk Among Patients With Myotonic Muscular Dystrophy

Gadalla¹,

Lund²,

Pfeiffer³

et al. 2011

JAMA

108

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Context Myotonic muscular dystrophy (MMD) is an autosomal dominant multisystem neuromuscular disorder characterized by unstable nucleotide repeat expansions. Case reports have suggested that MMD patients may be at increased risk of malignancy, putative risks which have never been quantified. Objective To quantitatively evaluate cancer risk in patients with MMD, overall, and by sex and age. Design, Setting, and Participants We identified 1,658 patients with an MMD discharge diagnosis in the Swedish Inpatient Hospital or Danish Patient Discharge Registries between 1977 and 2008. We linked these patients to their corresponding cancer registry. Patients were followed from date of first MMD-related inpatient or outpatient contact, to first cancer diagnosis, death, emigration, or completion of cancer registration. Main Outcome Measures Risks of all cancers combined, and by anatomic site, stratified by sex and age. Results 104 patients with an inpatient or outpatient discharge diagnosis of MMD developed cancer during post-discharge follow-up. This corresponds to an observed cancer rate of 73.4/10,000 person-years in MMD versus an expected rate of 36.9/10,000 in the general Swedish and Danish populations combined (SIR =2.0, 95% CI =1.6–2.4). Specifically, we observed significant excess risks of cancers of the endometrium (observed rate=16.1/10,000 person-years: SIR=7.6, 95%CI=4.0–13.2), brain (observed rate=4.9/10,000 person-years: SIR=5.3, 95%CI=2.3–10.4), ovary (observed rate=10.3/10,000 person-years: SIR=5.2, 95% CI=2.3–10.2), and colon (observed rate=7.1/10,000 person-years: SIR=2.9, 95%CI=1.5–5.1). Cancer risks were similar in females and males after excluding genital organ tumors (SIR=1.9, 95% CI=1.4–2.5 vs. 1.8, 95% CI=1.3–2.5, respectively, p-heterogeneity=0.81; observed rates=64.5 and 47.7/10,000 person-years in women and men, respectively), The same pattern of cancer excess was observed first in the Swedish, and then in the Danish cohorts, which were studied sequentially and initially analyzed independently. Conclusions MMD patients identified from the Swedish and Danish patient registries were at increased risk of cancer both overall and for selected anatomic sites.

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Differences in CTG triplet repeat expansion in leukemic cells and normal lymphocytes from a 14‐year‐old female with congenital myotonic dystrophy

Cited by 5 publications

References 18 publications

Frequency and type of cancers in myotonic dystrophy: A retrospective cross‐sectional study

Frequency and type of cancers in myotonic dystrophy: A retrospective cross‐sectional study

Correlates of tumor development in patients with myotonic dystrophy

Cancer Risk Among Patients With Myotonic Muscular Dystrophy

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