Oral squamous cell carcinoma in a patient with keratitis-ichthyosis-deafness syndrome: a rare case

Homeida, Lujain; Wiley, R. T.; Fatahzadeh, Mahnaz

doi:10.1016/j.oooo.2015.01.005

Cited by 9 publications

(7 citation statements)

References 24 publications

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“…GJB2, which encodes an epithelial gap junction protein, is mostly known for being associated with syndromic hearing loss, for example, keratitis-ichthyosis-deafness (KID). It has been reported that these KID patients with germline GJB2 mutation have increased risks of developing epithelial malignancies, for example, 19% occurrence of squamous cell carcinoma of the skin and oral mucosa compared to the normal population 13 . In total, combined with StJ cases, we detected seven GJB2 germline P/LP variants in C-AYA patients with CNS tumors (3 patients), osteosarcoma (2), Ewing sarcoma (1), and rhabdomyosarcoma (1).…”

Section: Resultsmentioning

confidence: 99%

Comprehensive germline genomic profiles of children, adolescents and young adults with solid tumors

et al. 2020

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Compared to adult carcinomas, there is a paucity of targeted treatments for solid tumors in children, adolescents, and young adults (C-AYA). The impact of germline genomic signatures has implications for heritability, but its impact on targeted therapies has not been fully appreciated. Performing variant-prioritization analysis on germline DNA of 1,507 C-AYA patients with solid tumors, we show 12% of these patients carrying germline pathogenic and/ or likely pathogenic variants (P/LP) in known cancer-predisposing genes (KCPG). An additional 61% have germline pathogenic variants in non-KCPG genes, including PRKN, SMAR-CAL1, SMAD7, which we refer to as candidate genes. Despite germline variants in a broad gene spectrum, pathway analysis leads to top networks centering around p53. Our drugtarget analysis shows 1/3 of patients with germline P/LP variants have at least one druggable alteration, while more than half of them are from our candidate gene group, which would otherwise go unidentified in routine clinical care.

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Section: Resultsmentioning

confidence: 99%

Comprehensive germline genomic profiles of children, adolescents and young adults with solid tumors

et al. 2020

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“…The chronic skin inflammation associated with the F142L mutation suggested similarities to KID syndrome where patients, including those with the G12R mutation, are also susceptible to severe bacterial and fungal infections. [1,[26][27][28][29] "Leaky" hemichannels, with altered gating characteristics, are proposed to be a causative event in the progression of KID syndrome. [8,9,16,[30][31][32] Each KID mutation studied to date has unique characteristics rendering the channels more sensitive to changes in calcium, zinc and other ions and are influenced by pro-inflammatory mediators such as peptidoglycan a key component of gram-positive bacterial cell wall, [8,9,16,31,32] with several mutations resulting in lethal phenotypes.…”

Section: Discussionmentioning

confidence: 99%

A heterozygous mutation in GJB2 (Cx26F142L) associated with deafness and recurrent skin rashes results in connexin assembly deficiencies

Albuloushi

Lovgren

Steel

et al. 2020

Experimental Dermatology

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Mutations in GJB2 encoding Connexin 26 (CX26) are associated with hearing loss and hyperproliferative skin disorders of differing severity including keratitis‐ichthyosis‐deafness (KID) and Vohwinkel syndrome. A 6‐year‐old Caucasian girl who presented with recurrent skin rashes and sensorineural hearing loss harboured a heterozygous point mutation in GJB2 (c.424T > C; p.F142L). To characterize the impact of CX26F142L on cellular events. Plasmids CX26WT, CX26F142L, CX26G12R (KID) or CX26D66H (Vohwinkel) were transfected into HeLa cells expressing Cx26 or Cx43 or into HaCaT cells, a model keratinocyte cell line. Confocal microscopy determined protein localization. MTT assays assessed cell viability in the presence or absence of carbenoxolone, a connexin‐channel blocker. Co‐immunoprecipitation/Western blot analysis determined Cx43:Cx26 interactions. Quantitative real‐time polymerase chain reaction assessed changes in gene expression of ER stress markers. Dye uptake assays determined Connexin‐channel functionality. F142L and G12R were restricted to perinuclear areas. Collapse of the microtubule network, rescued by co‐treatment with paclitaxel, occurred. ER stress was not involved. Cell viability was reduced in cells expressing F142L and G12R but not D66H. Unlike G12R that forms “leaky” hemichannels, F142L had restricted permeability. Cell viability of F142L and G12R transfected cells was greater in HeLa cells expressing Cx43 than in native Cx‐free HeLa cells. Co‐immunoprecipitation suggested a possible interaction between Cx43 and the three mutations. Expression of CX26F142L and G12R results in microtubule collapse, rescued by interaction with Cx43. The GJB2 mutations interacted with Cx43 suggesting that unique Cx43:Cx26 channels are central to the diverse phenotype of CX26 skin‐related channelopathies.

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“…Connexin mutations increase hemichannel activity and cell death has been described. 3 However, more research is needed to associate increased hemichannel activity with pathological changes in the epidermis.To the best of our knowledge, including this case, there have been 20 KID syndrome with squamous cell carcinoma (SCC) 1,4 and this is the first report of Chinese patients presenting with SCC. Cx26 has also been suspected to be a tumorsuppressor gene that is responsible for the development, growth and differentiation in epithelial tissues.…”

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confidence: 81%

“…Cx26 has also been suspected to be a tumorsuppressor gene that is responsible for the development, growth and differentiation in epithelial tissues. 5 In addition, chronic skin irritation, bacterial superinfection and proliferative epidermal growth may be reasons for the establishment of skin cancer, 4 so a life-long follow up is necessary for patients suffering from this disease. Reversible skin and hair depigmentation during chemotherapy with dasatinib for chronic myeloid leukemia Dear Editor, Dasatinib, a second-generation Bcr-Abl tyrosine kinase inhibitor (TKI), is the first-choice drug for treating the chronic, accelerated and blastic phases of chronic myeloid leukemia (CML).…”

Section: Mutations Of Connexin 26 (Gjb2) Gene In a Chinese Keratitisimentioning

confidence: 99%

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Mutations of connexin 26 (GJB2) gene in a Chinese keratitis–ichthyosis–deafness syndrome patient with squamous cell carcinoma

Liu

Fang

Ding

et al. 2015

The Journal of Dermatology

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Detailed examination revealed delayed eruption of teeth, a cerebral arachnoid cyst ( Fig. 1e) and optic atrophy on her left hemicorpus. After obtaining informed consent under institutional approval and in adherence to the principles of the Declaration of Helsinki, genomic DNA was separately extracted from the KEN-like lesional epidermis/dermis and non-lesional epidermis of the patient. Each exon of the HRAS and KRAS genes was amplified by polymerase chain reaction using specific primer pairs, 1 and the direct sequencing revealed a missense mutation of KRAS c.34G>T (p.G12C) in the lesional epidermis but not in lesional dermis, non-lesional epidermis or parental blood DNA (Fig. 1f).Immunohistochemical staining showed increased nuclear distribution of phosphorylated extracellular signal-regulated kinase (ERK) in both the epidermis and sebaceous glands of lesional skin (Fig. 1g, arrowheads). These clinical and histopathological findings led to the diagnosis of ENS. Mutations in the 12th codon result in constitutive activation of KRAS.4 According to the COSMIC database, the KRAS c.34G>T mutation has been described as an oncogenic mutation in various carcinomas. To our knowledge, this is the first report describing a case of ENS with this mutation. As the mutation and activation of ERK, one of main mediators in downstream KRAS signaling, were specifically detected in the lesional epidermis, we assumed that KRAS c.34G>T resulted in increased tissue proliferation. While there is no effective treatment for ENS at present, the molecular mechanism suggests a potency of treatment using signal inhibitors. The appearance of skin lesions can be a major ENS-related problem for cosmetic reasons. Therefore, topical application of these chemicals may be as therapeutically promising as rapamycin used for skin lesions found in tuberous sclerosis. Mutations of connexin 26 (GJB2) gene in a Chinese keratitisichthyosis-deafness syndrome patient with squamous cell carcinomaDear Editor, We report a 36-year-old Chinese woman with typical features of keratitis-ichthyosis-deafness (KID) syndrome. The woman was found to have generalized "leather-like" thickened skin and xeroderma (Fig. 1a,b). Radial striations were found around the mouth because of severe hyperkeratosis and dryness (Fig. 1e). She also had hypotrichosis (no scalp hair, eyebrows or eyelashes) and nail dystrophy (Fig. 1c,d). She had also been previously diagnosed with bilateral sensorineural deafness and keratitis. An approximately 10 cm 9 12 cm, exophytic, crust-covered, tumorous mass was especially prominent on the left leg (Fig. 1f). She was born at term and psychomotor development was normal. A skin biopsy from her abdomen showed hyperkeratosis and parakeratosis, reduced granular layer and acanthosis in the epidermis, and a slight perivascular lymphocytic infiltration was evident in the © 2015 Japanese Dermatological AssociationLetters to the Editor dermis (Fig. 1g). Histopathology of her left leg revealed a tumorous mass containing squamous epithelial cells located in the...

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Oral squamous cell carcinoma in a patient with keratitis-ichthyosis-deafness syndrome: a rare case

Cited by 9 publications

References 24 publications

Comprehensive germline genomic profiles of children, adolescents and young adults with solid tumors

Comprehensive germline genomic profiles of children, adolescents and young adults with solid tumors

A heterozygous mutation in GJB2 (Cx26F142L) associated with deafness and recurrent skin rashes results in connexin assembly deficiencies

Mutations of connexin 26 (GJB2) gene in a Chinese keratitis–ichthyosis–deafness syndrome patient with squamous cell carcinoma

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