Mutation analysis of multiple pilomatricomas in a patient with myotonic dystrophy type 1 suggests a DM1-associated hypermutation phenotype

Rübben, Albert; Wahl, R.U.; Eggermann, Thomas; Dahl, Edgar; Ortiz-Brüchle, Nadina; Cacchi, Claudio

doi:10.1371/journal.pone.0230003

Cited by 16 publications

(12 citation statements)

References 40 publications

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“…Malignant pilomatricoma (MP), a very rare adnexal cancer with a high rate of local recurrence but uncommon distant metastasis, has not been extensively characterized at the molecular level. To date, CTNNB1, the gene encoding βcatenin, is the only driver mutation identified in both benign and MPs (3,13). Magdalena et al as well as Katharina et al have reported a few pediatric cases of multiple pilomatricoma with CTNNB1 mutations, associated with germline mutations in mismatch repair genes (14,15).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Benign and Malignant Pilomatricomas Using Whole-exome Sequencing

Yeo

Bae

2020

Cancer Genomics Proteomics

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Background: Malignant pilomatricoma (MP) is a rare cancer of the hair matrix with only a few cases reported in literature. Given the rarity of this cancer and the lack of relevant genetic data, very little is known about the nature of the molecular pathophysiology except the involvement of the Catenin Beta 1 (CTNNB1)/Wnt/β-catenin signaling pathway in some cases. Materials and Methods: We describe the whole-exome genomic profiling of four samples from two patients: 1) an MP from patient I, 2) a coexisting benign pilomatricoma (BP) from patient I, 3) a BP from an age and location-matched control patient II, and 4) normal skin tissue from patient II. Results: We detected a pathogenic somatic missense mutation in fibroblast growth factor receptor 4 (FGFR4) (c.1162G>A, p. Gly388Arg) in MP and coexisting BP in patient I, whereas the control BP harbored the classical CTNNB1 mutant. Conclusion: This study, the first comparative analysis of benign and MP through whole-exome analysis, identified a novel oncogenic mutation in FGFR4. Malignant pilomatricomas (MPs) are extremely rare adnexal cancers originating from hair matrix cells. Fewer than 150 cases of MPs have been reported in literature worldwide and the vast majority as case reports (1-4). MP has significant recurrence and metastatic potential, but due to its slow growth and rarity, it is often clinically misdiagnosed as a sebaceous cyst or other common skin tumor, potentially delaying tumor resection (4). MP can arise de novo as a solitary lesion or through the transformation of a benign pilomatricoma (BP); however, no available immunohistochemical or molecular methods are capable of distinguishing BP from MP.

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Section: Discussionmentioning

confidence: 99%

Comparison of Benign and Malignant Pilomatricomas Using Whole-exome Sequencing

Yeo

Bae

2020

Cancer Genomics Proteomics

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“…These lesions are typically firm, slow‐growing nodules located on the head, neck, and extremities of children and young adults 1,2 . Multiple pilomatricomas have been recognized in patients with complex conditions including Gardner syndrome, Rubinstein‐Taybi syndrome, myotonic dystrophy, Kabuki syndrome, and trisomy 9 3,4 …”

Section: Discussionmentioning

confidence: 99%

“…1,2 Multiple pilomatricomas have been recognized in patients with complex conditions including Gardner syndrome, Rubinstein-Taybi syndrome, myotonic dystrophy, Kabuki syndrome, and trisomy 9. 3,4 Proliferating pilomatricoma is a rare variant, appearing as a rapidly growing, vascular lesion in elderly patients. They initially appear as solitary, acnelike papules that quickly evolve into large, vascular nodules or tumors.…”

Section: Discussionmentioning

confidence: 99%

Proliferating pilomatricoma in a 9‐year‐old girl

McCormack

Trivedi

Lal

et al. 2020

Pediatric Dermatology

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“…In mismatch repair deficiency or myotonic dystrophy, hypermutation phenotypes lead to secondary somatic mutations of CTNNB1 that result in formation of multiple pilomatricomas (Table 3, Figure 2G). 21,22 …”

Section: Tumours With Follicular Differentiationmentioning

confidence: 99%

Molecular pathology of skin adnexal tumours

2021

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Aims Tumours of the cutaneous adnexa arise from, or differentiate towards, structures in normal skin such as hair follicles, sweat ducts/glands, sebaceous glands or a combination of these elements. This class of neoplasms includes benign tumours and highly aggressive carcinomas. Adnexal tumours often present as solitary sporadic lesions, but can herald the presence of an inherited tumour syndrome such as Muir–Torre syndrome, Cowden syndrome or CYLD cutaneous syndrome. In contrast to squamous cell carcinoma and basal cell carcinoma, molecular changes in adnexal neoplasia have been poorly characterised and there are few published reviews on the current state of knowledge. Methods and results We reviewed findings in peer‐reviewed literature on molecular investigations of cutaneous adnexal tumours published to June 2021. Conclusions Recent discoveries have revealed diverse oncogenic drivers and tumour suppressor alterations in this class of tumours, implicating pathways including Ras/MAPK, PI3K, YAP/TAZ, beta‐catenin and nuclear factor kappa B (NF‐κB). These observations have identified novel markers, such as NUT for poroma and porocarcinoma and PLAG1 for mixed tumours. Here, we provide a comprehensive overview and update of the molecular findings associated with adnexal tumours of the skin.

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Mutation analysis of multiple pilomatricomas in a patient with myotonic dystrophy type 1 suggests a DM1-associated hypermutation phenotype

Cited by 16 publications

References 40 publications

Comparison of Benign and Malignant Pilomatricomas Using Whole-exome Sequencing

Comparison of Benign and Malignant Pilomatricomas Using Whole-exome Sequencing

Proliferating pilomatricoma in a 9‐year‐old girl

Molecular pathology of skin adnexal tumours

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