Coding and noncoding somatic mutations in candidate genes in basal cell carcinoma

Basal cell carcinoma (BCC) is a significant public health concern, with more than 3 million cases occurring each year in the United States, and with an increasing incidence. The molecular basis of BCC is complex, involving an interplay of inherited genetic susceptibility, including single nucleotide polymorphisms and genetic syndromes, and sporadic somatic mutations, often induced by carcinogenic exposure to UV radiation. This review outlines the currently known germline and somatic mutations implicated in the pathogenesis of BCC, including the key molecular pathways affected by these mutations, which drive oncogenesis. With advances in next generation sequencing and our understanding of the molecular genetics of BCC, established and emerging targeted therapeutics are offering new avenues for the non-surgical treatment of BCC. These agents, including Hedgehog pathway inhibitors, immune modulators, and histone deacetylase inhibitors, will also be discussed.

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Novel alterations in IFT172 and KIFAP3 may induce basal cell carcinoma

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-02033-7 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Shoko Onodera ◽

Nana Morita ◽

Yuriko Nakamura ◽

Shinichi Takahashi ◽

Kazuhiko Hashimoto ◽

...

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Somatic Mutations ◽

Enrichment Analysis ◽

Sequencing Analysis ◽

Gorlin Syndrome ◽

Driver Genes ◽

Aged Patients ◽

Basal Cell Carcinomas

Abstract Background Basal cell carcinoma (BCC) is the most commonly occurring neoplasm in patients with Gorlin syndrome. It is widely accepted that multiple basal cell carcinomas simultaneously develop in middle-aged patients with this syndrome. However, the presence of driver genes other than the PTCH1 in Gorlin syndrome has not been explored. This study aimed to identify common gene mutations other than PTCH1 in simultaneously occurring basal cell carcinomas in patients with Gorlin syndrome via exome sequencing analysis. Methods Next-generation sequencing analysis was performed using four basal cell carcinoma samples, one dental keratinocyte sample, and two epidermoid cyst samples, which were surgically resected from one patient with Gorlin syndrome on the same day. Results Overall, 282 somatic mutations were identified in the neoplasms. No additional somatic mutations in PTCH1, PTCH2, TP53, and SMO were identified. However, enrichment analysis showed that multiple genes, such as IFT172 and KIFAP3, could regulate ciliary functions important for Hedgehog signaling. Conclusion The development of BCCs in patients with Gorlin syndrome may be triggered by mutations that cause substantial dysfunction of cilia.

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Multiple basal cell carcinoma in lymphoedema

Phlebologie ◽

10.1055/s-0037-1622128 ◽

2006 ◽

Vol 35 (01) ◽

pp. 30-33

Author(s):

I. Wollmer ◽

J. Wenzel ◽

E. Rabe ◽

F. Pannier ◽

K. Hamm

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Somatic Mutations ◽

Skin Lesions ◽

Cell Trafficking ◽

Skin Damage ◽

Predisposing Factor ◽

Malignant Skin ◽

History Of

SummaryBasal cell carcinoma is the most common malignant skin tumour, but rarely appears in more than one location. For these multiple basal cell carcinoma (MBCC), lymphoedema seems to be a predisposing factor. We report the case of a patient with secondary lymphoedema, presenting with a 3-year-history of ulcerations and papules on her lymphoedematous leg. Histology confirmed the clinical diagnosis of MBCC in all lesions.Pathophysiologically, a strong risk factor for the development of MBCC in lymphoedema seems to be the local failure of immunosurveillance. In obstructive lymphoedema, an impairment of lymphocyte and Langerhans cell trafficking was observed, resulting in ineffective phagocytosis of foreign antigens. Consequently, lymphoedema is an immunologically vulnerable area, facilitating the development of MBCC. Nevertheless, other risk factors such as actinic skin damage and somatic mutations might also play a role in the development of MBCC in lymphoedema. Despite its rare occurrence, MBCC has to be taken into consideration in all suspicious skin lesions. Whenever in doubt, skin biopsy should be performed.

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Ultrastructure of Mouse Basal Cell Carcinoma Exhibiting Sebaceous Differentiation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600003214 ◽

1980 ◽

Vol 38 ◽

pp. 738-739

Author(s):

Victoria L. Wade ◽

Winslow G. Sheldon ◽

James W. Townsend ◽

William Allaben

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Topical Application ◽

Basal Cell ◽

Sebaceous Gland ◽

Rats And Mice ◽

Mixed Tumors

Sebaceous gland tumors and other tumors exhibiting sebaceous differentiation have been described in humans (1,2,3). Tumors of the sebaceous gland can be induced in rats and mice following topical application of carcinogens (4), but spontaneous mixed tumors of basal cell origin rarely occur in mice.

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