Novel Alterations in IFT172 and KIFAP3 May Induce Basal Cell Carcinoma

Overview

Journal Orphanet J Rare Dis

Publisher Biomed Central

Specialty General Medicine

Date 2021 Oct 22

PMID 34674729

Citations 2

Authors

Shoko Onodera

Nana Morita

Yuriko Nakamura

Shinichi Takahashi

Kazuhiko Hashimoto

Takeshi Nomura

Akira Katakura

Kenjiro Kosaki

Toshifumi Azuma

Affiliations

Soon will be listed here.

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.

Citing Articles

PABPN1 functions as a predictive biomarker in colorectal carcinoma.

Wang Q, Yan P, Shi L, Teng Y, Gao X, Yao L Mol Biol Rep. 2023; 51(1):40.

PMID: 38158471 DOI: 10.1007/s11033-023-08936-x.

Comprehensive analysis of circRNAs for N7-methylguanosine methylation modification in human oral squamous cell carcinoma.

Sun D, Song N, Li M, Chen X, Zhang X, Yu Y FASEB Bioadv. 2023; 5(8):305-320.

PMID: 37554544 PMC: 10405248. DOI: 10.1096/fba.2023-00036.

References

Li H, Durbin R . Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009; 25(14):1754-60. PMC: 2705234. DOI: 10.1093/bioinformatics/btp324. View

Carpenter B, Barry R, Verhey K, Allen B . The heterotrimeric kinesin-2 complex interacts with and regulates GLI protein function. J Cell Sci. 2015; 128(5):1034-50. PMC: 4342584. DOI: 10.1242/jcs.162552. View

Lek M, Karczewski K, Minikel E, Samocha K, Banks E, Fennell T . Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016; 536(7616):285-91. PMC: 5018207. DOI: 10.1038/nature19057. View

Schwarz J, Rodelsperger C, Schuelke M, Seelow D . MutationTaster evaluates disease-causing potential of sequence alterations. Nat Methods. 2010; 7(8):575-6. DOI: 10.1038/nmeth0810-575. View

Tamaki T, Dong Y, Ohno Y, Sobue T, Nishimoto H, Shibata A . The burden of rare cancer in Japan: application of the RARECARE definition. Cancer Epidemiol. 2014; 38(5):490-5. DOI: 10.1016/j.canep.2014.07.014. View

He M, Agbu S, Anderson K . Microtubule Motors Drive Hedgehog Signaling in Primary Cilia. Trends Cell Biol. 2016; 27(2):110-125. PMC: 5258846. DOI: 10.1016/j.tcb.2016.09.010. View

San Lucas F, Wang G, Scheet P, Peng B . Integrated annotation and analysis of genetic variants from next-generation sequencing studies with variant tools. Bioinformatics. 2011; 28(3):421-2. PMC: 3268240. DOI: 10.1093/bioinformatics/btr667. View

Yoshida J, Tsuneyoshi M, Nakamura K, Murakami T, Akamine Y . Primary ciliary dyskinesia with transverse colon carcinoma. Am J Clin Pathol. 1986; 85(1):101-4. DOI: 10.1093/ajcp/85.1.101. View

Hahn H, Wicking C, Zaphiropoulous P, Gailani M, Shanley S, Chidambaram A . Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell. 1996; 85(6):841-51. DOI: 10.1016/s0092-8674(00)81268-4. View

10.

Eggenschwiler J, Anderson K . Cilia and developmental signaling. Annu Rev Cell Dev Biol. 2007; 23:345-73. PMC: 2094042. DOI: 10.1146/annurev.cellbio.23.090506.123249. View

11.

Onodera S, Saito A, Hasegawa D, Morita N, Watanabe K, Nomura T . Multi-layered mutation in hedgehog-related genes in Gorlin syndrome may affect the phenotype. PLoS One. 2017; 12(9):e0184702. PMC: 5600381. DOI: 10.1371/journal.pone.0184702. View

12.

Wang Q, Taschner M, Ganzinger K, Kelley C, Villasenor A, Heymann M . Membrane association and remodeling by intraflagellar transport protein IFT172. Nat Commun. 2018; 9(1):4684. PMC: 6224603. DOI: 10.1038/s41467-018-07037-9. View

13.

McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A . The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010; 20(9):1297-303. PMC: 2928508. DOI: 10.1101/gr.107524.110. View

14.

Heffelfinger C, Ouyang Z, Engberg A, Leffell D, Hanlon A, Gordon P . Correlation of Global MicroRNA Expression With Basal Cell Carcinoma Subtype. G3 (Bethesda). 2012; 2(2):279-86. PMC: 3284335. DOI: 10.1534/g3.111.001115. View

15.

Gatta G, van der Zwan J, Casali P, Siesling S, Dei Tos A, Kunkler I . Rare cancers are not so rare: the rare cancer burden in Europe. Eur J Cancer. 2011; 47(17):2493-511. DOI: 10.1016/j.ejca.2011.08.008. View

16.

Maturo M, Rachakonda S, Heidenreich B, Pellegrini C, Srinivas N, Requena C . Coding and noncoding somatic mutations in candidate genes in basal cell carcinoma. Sci Rep. 2020; 10(1):8005. PMC: 7224188. DOI: 10.1038/s41598-020-65057-2. View

17.

Cooper G, Stone E, Asimenos G, Green E, Batzoglou S, Sidow A . Distribution and intensity of constraint in mammalian genomic sequence. Genome Res. 2005; 15(7):901-13. PMC: 1172034. DOI: 10.1101/gr.3577405. View

18.

Rentzsch P, Witten D, Cooper G, Shendure J, Kircher M . CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res. 2018; 47(D1):D886-D894. PMC: 6323892. DOI: 10.1093/nar/gky1016. View

19.

Corbit K, Aanstad P, Singla V, Norman A, Stainier D, Reiter J . Vertebrate Smoothened functions at the primary cilium. Nature. 2005; 437(7061):1018-21. DOI: 10.1038/nature04117. View

20.

Giglia-Mari G, Sarasin A . TP53 mutations in human skin cancers. Hum Mutat. 2003; 21(3):217-28. DOI: 10.1002/humu.10179. View