scholarly journals 483 Next-generation target sequencing analysis identifies multiple somatic mutations in basal cell carcinoma

2019 ◽  
Vol 139 (9) ◽  
pp. S297
Author(s):  
L. Di Nardo ◽  
C. Pellegrini ◽  
M. Maturo ◽  
F. Ricci ◽  
A. Di Stefani ◽  
...  
2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shoko Onodera ◽  
Nana Morita ◽  
Yuriko Nakamura ◽  
Shinichi Takahashi ◽  
Kazuhiko Hashimoto ◽  
...  

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.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3870
Author(s):  
James M. Kilgour ◽  
Justin L. Jia ◽  
Kavita Y. Sarin

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.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Maria Giovanna Maturo ◽  
Sivaramakrishna Rachakonda ◽  
Barbara Heidenreich ◽  
Cristina Pellegrini ◽  
Nalini Srinivas ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Rachel Y. Chow ◽  
Ung Seop Jeon ◽  
Taylor M. Levee ◽  
Gurleen Kaur ◽  
Daniel P. Cedeno ◽  
...  

Basal cell carcinoma (BCC) is a locally invasive epithelial cancer that is primarily driven by the Hedgehog (HH) pathway. Advanced BCCs are a critical subset of BCCs that frequently acquire resistance to Smoothened (SMO) inhibitors and identifying pathways that bypass SMO could provide alternative treatments for patients with advanced or metastatic BCC. Here, we use a combination of RNA-sequencing analysis of advanced human BCC tumor-normal pairs and immunostaining of human and mouse BCC samples to identify a PI3K pathway expression signature in BCC. Pharmacological inhibition of PI3K activity in BCC cells significantly reduces cell proliferation and HH signaling. However, treatment of Ptch1fl/fl; Gli1-CreERT2 mouse BCCs with the PI3K inhibitor BKM120 results in a reduction of tumor cell growth with no significant effect on HH signaling. Downstream PI3K components aPKC and Akt1 showed a reduction in active protein, whereas their substrate, cyclin-dependent kinase inhibitor p21, showed a concomitant increase in protein stability. Our results suggest that PI3K promotes BCC tumor growth by kinase-induced p21 degradation without altering HH signaling.


Phlebologie ◽  
2006 ◽  
Vol 35 (01) ◽  
pp. 30-33
Author(s):  
I. Wollmer ◽  
J. Wenzel ◽  
E. Rabe ◽  
F. Pannier ◽  
K. Hamm

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.


Author(s):  
Victoria L. Wade ◽  
Winslow G. Sheldon ◽  
James W. Townsend ◽  
William Allaben

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.


2000 ◽  
Vol 39 (5) ◽  
pp. 397-398 ◽  
Author(s):  
Hyoung-Joo Kim ◽  
Youn-Soo Kim ◽  
Ki-Beom Suhr ◽  
Tae-Young Yoon ◽  
Jeung-Hoon Lee ◽  
...  

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