scholarly journals BIRC2–BIRC3 amplification: a potentially druggable feature of a subset of head and neck cancers in patients with Fanconi anemia

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Khashayar Roohollahi ◽  
Yvonne de Jong ◽  
Govind Pai ◽  
Mohamad Amr Zaini ◽  
Klaas de Lint ◽  
...  
Keyword(s):  
Head And Neck ◽  
Fanconi Anemia ◽  
Chromosomal Instability ◽  
Squamous Cell Carcinomas ◽  
Copy Number Alterations ◽  
Suitable Alternative ◽  
Drug Concentrations ◽  
Whole Exome ◽  
Molecule Inhibitor ◽  
Somatic Hypersensitivity

AbstractHead-and-neck squamous cell carcinomas (HNSCCs) are relatively common in patients with Fanconi anemia (FA), a hereditary chromosomal instability disorder. Standard chemo-radiation therapy is not tolerated in FA due to an overall somatic hypersensitivity to such treatment. The question is how to find a suitable alternative treatment. We used whole-exome and whole genome mRNA sequencing to identify major genomic and transcriptomic events associated with FA-HNSCC. CRISPR-engineered FA-knockout models were used to validate a number of top hits that were likely to be druggable. We identified deletion of 18q21.2 and amplification of 11q22.2 as prevailing copy-number alterations in FA HNSCCs, the latter of which was associated with strong overexpression of the cancer-related genes YAP1, BIRC2, BIRC3 (at 11q22.1-2). We then found the drug AZD5582, a known small molecule inhibitor of BIRC2-3, to selectively kill FA tumor cells that overexpressed BIRC2-3. This occurred at drug concentrations that did not affect the viability of untransformed FA cells. Our data indicate that 11q22.2 amplifications are relatively common oncogenic events in FA-HNSCCs, as holds for non FA-HNSCC. Therefore, chemotherapeutic inhibition of overexpressed BIRC2-3 may provide the basis for an approach to develop a clinically realistic treatment of FA-HNSCCs that carry 11q22.2 amplifications.

scholarly journals Genome-wide DNA copy number alterations in head and neck squamous cell carcinomas with or without oncogene-expressing human papillomavirus

Oncogene ◽  
2005 ◽  
Vol 25 (17) ◽  
pp. 2558-2564 ◽  
Author(s):  
S J Smeets ◽  
B J M Braakhuis ◽  
S Abbas ◽  
P J F Snijders ◽  
B Ylstra ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Head And Neck ◽  
Squamous Cell ◽  
Copy Number ◽  
Squamous Cell Carcinomas ◽  
Copy Number Alterations ◽  
Dna Copy Number ◽  
Genome Wide ◽  
Dna Copy Number Alterations

Abstract LB-398: Detection of copy number alterations in 124 head and neck squamous cell carcinomas using the Nanostring nCounter assay

2012 ◽  
Author(s):  
Michaela Kristina Keck ◽  
Zhixiang Zuo ◽  
Arun Khattri ◽  
Johannes Braegelmann ◽  
Mark Lingen ◽  
...  
Keyword(s):  
Head And Neck ◽  
Squamous Cell ◽  
Copy Number ◽  
Squamous Cell Carcinomas ◽  
Copy Number Alterations

scholarly journals Squamous Cell Carcinomas of the Head and Neck in Fanconi Anemia: Risk, Prevention, Therapy, and the Need for Guidelines

2012 ◽  
Vol 224 (03) ◽  
pp. 132-138 ◽  
Author(s):  
K. Scheckenbach ◽  
M. Wagenmann ◽  
M. Freund ◽  
J. Schipper ◽  
H. Hanenberg
Keyword(s):  
Head And Neck ◽  
Squamous Cell ◽  
Fanconi Anemia ◽  
Squamous Cell Carcinomas ◽  
Risk Prevention ◽  
Prevention Therapy

GENIPAC: A Genomic Information Portal for Head and Neck Cancer Cell Systems

2018 ◽  
Vol 97 (8) ◽  
pp. 909-916 ◽  
Author(s):  
B.K.B. Lee ◽  
C.P. Gan ◽  
J.K. Chang ◽  
J.L. Tan ◽  
M.Z. Fadlullah ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Exome Sequencing ◽  
Cell Lines ◽  
Copy Number ◽  
Rna Seq ◽  
Copy Number Alterations ◽  
Genomic Information ◽  
Genomic Alterations ◽  
Whole Exome

Head and neck cancer (HNC)–derived cell lines represent fundamental models for studying the biological mechanisms underlying cancer development and precision therapies. However, mining the genomic information of HNC cells from available databases requires knowledge on bioinformatics and computational skill sets. Here, we developed a user-friendly web resource for exploring, visualizing, and analyzing genomics information of commonly used HNC cell lines. We populated the current version of GENIPAC with 44 HNC cell lines from 3 studies: ORL Series, OPC-22, and H Series. Specifically, the mRNA expressions for all the 3 studies were derived with RNA-seq. The copy number alterations analysis of ORL Series was performed on the Genome Wide Human Cytoscan HD array, while copy number alterations for OPC-22 were derived from whole exome sequencing. Mutations from ORL Series and H Series were derived from RNA-seq information, while OPC-22 was based on whole exome sequencing. All genomic information was preprocessed with customized scripts and underwent data validation and correction through data set validator tools provided by cBioPortal. The clinical and genomic information of 44 HNC cell lines are easily assessable in GENIPAC. The functional utility of GENIPAC was demonstrated with some of the genomic alterations that are commonly reported in HNC, such as TP53, EGFR, CCND1, and PIK3CA. We showed that these genomic alterations as reported in The Cancer Genome Atlas database were recapitulated in the HNC cell lines in GENIPAC. Importantly, genomic alterations within pathways could be simultaneously visualized. We developed GENIPAC to create access to genomic information on HNC cell lines. This cancer omics initiative will help the research community to accelerate better understanding of HNC and the development of new precision therapeutic options for HNC treatment. GENIPAC is freely available at http://genipac.cancerresearch.my/ .

scholarly journals Cancer stem cells are enriched in Fanconi anemia head and neck squamous cell carcinomas

2014 ◽  
Vol 45 (6) ◽  
pp. 2365-2372 ◽  
Author(s):  
JEAN WU ◽  
QINGSHAN MU ◽  
VARATHARASA THIVIYANATHAN ◽  
ANANTH ANNAPRAGADA ◽  
NADARAJAH VIGNESWARAN
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Head And Neck ◽  
Squamous Cell ◽  
Fanconi Anemia ◽  
Squamous Cell Carcinomas

Smoking correlates with the presence of p53 mutations in squamous cell carcinomas of the head and neck (SCCHN)

1998 ◽  
Vol 23 (3) ◽  
pp. 268-269
Author(s):  
Liloglou ◽  
Scholes ◽  
Spandidos ◽  
Jones ◽  
Vaughan ◽  
...  
Keyword(s):  
Head And Neck ◽  
Squamous Cell ◽  
Squamous Cell Carcinomas ◽  
P53 Mutations

Identification of the Genomic Structure of Tumor Suppressor ING1 and Mutation Analysis in Head and Neck Squamous Cell Carcinomas

2005 ◽  
Vol 14 (2) ◽  
pp. 320-321
Author(s):  
Mehmet Gunduz ◽  
Esra Gunduz ◽  
Byung-Moo Min ◽  
Gene Lee ◽  
Ji-Jun Lim ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Head And Neck ◽  
Mutation Analysis ◽  
Squamous Cell ◽  
Genomic Structure ◽  
Squamous Cell Carcinomas
Sign in / Sign up

Export Citation Format

Share Document