The genomic landscape of UM-SCC oral cavity squamous cell carcinoma cell lines

Ludwig, Megan; Kulkarni, Aditi; Birkeland, Andrew C.; Michmerhuizen, Nicole L.; Foltin, Susan K.; Mann, Jacqueline E.; Hoesli, Rebecca C.; Devenport, Samantha; Jewell, Brittany M.; Shuman, Andrew G.; Spector, Matthew E.; Carey, Thomas E.; Jiang, Hui; Brenner, J. Chad

doi:10.1016/j.oraloncology.2018.10.031

Cited by 30 publications

(33 citation statements)

References 44 publications

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“…The same group further reported a higher frequency (21%) of PIK3CA mutation in tumors of mixed origin [85]. The mutational frequency of PIK3CA varied between types of HNSCC: oral squamous cell carcinomas (OSCC: 21% in cell lines and 17% in of primary tumors) [86]; nasopharyngeal carcinomas (10%; [87]); and head and neck cancer cell lines (30%; [88]). PIK3CA gene amplifications were also reported in oral cavity cancer cell lines [89].…”

Section: Pik3ca Gene Mutations Frequency In Head and Neck Squamous Cementioning

confidence: 86%

PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis

Alqahtani

Ayesh

Halawani

2019

Cancers

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Phosphoinositide kinases (PIKs) are a group of lipid kinases that are important upstream activators of various significant signaling pathways. Hyperactivation of the PI3K/AKT/mTOR pathways—either via mutations or genomic amplification—confers key oncogenic activity, essential for the development and progression of several solid tumors. Alterations in the PIK3CA gene are associated with poor prognosis of solid malignancies. Although the literature reports contradictory prognostic values of PIK3CA in aggressive cancers, most of the available data highlight the important role of PIK3CA mutation in mediating tumorigenesis via increased signaling of the PI3K/AKT/mTOR survival pathway. Several inhibitors of PI3K/AKT/mTOR pathways are investigated as potential therapeutic options in solid malignancies. This article reviews the role of PIK3CA mutations and inhibitors of PI3K/AKT/mTOR pathways in major cancer types and examines its association with clinicopathological parameters and prognosis.

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Section: Pik3ca Gene Mutations Frequency In Head and Neck Squamous Cementioning

confidence: 86%

PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis

Alqahtani

Ayesh

Halawani

2019

Cancers

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“…30,[34][35][36] In a recent study, Signature 4 was found mainly in cancers derived from epithelia directly exposed to tobacco smoke and was most abundant in lung and laryngeal cancers. 29 HPV-negative HNSCC 13,[37][38][39][40] and with a poor prognosis. 41,42 CDKN2A is a well-established tumor suppressor gene in squamous cell carcinoma and other types of human cancer.…”

Section: Discussionmentioning

confidence: 99%

Unraveling most abundant mutational signatures in head and neck cancer

Plath

Gass

Hlevnjak

et al. 2020

Intl Journal of Cancer

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Genomic alterations are a driving force in the multistep process of head and neck cancer (HNC) and result from the interaction of exogenous environmental exposures and endogenous cellular processes. Each of these processes leaves a characteristic pattern of mutations on the tumor genome providing the unique opportunity to decipher specific signatures of mutational processes operative during HNC pathogenesis and to address their prognostic value. Computational analysis of whole exome sequencing data of the HIPO-HNC (Heidelberg Center for Personalized Oncologyhead and neck cancer) (n = 83) and TCGA-HNSC (The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma) (n = 506) cohorts revealed five common mutational signatures (Catalogue of Somatic Mutations in Cancer [COSMIC] Signatures 1, 2, 3, 13 and 16) and demonstrated their significant association with etiological risk factors (tobacco, alcohol and HPV16). Unsupervised hierarchical clustering identified four clusters (A, B, C1 and C2) of which Subcluster C2 was enriched for cases with a higher frequency of signature 16 mutations. Tumors of Subcluster C2 had significantly lower p16 INK4A expression accompanied by homozygous CDKN2A deletion in almost one half of cases. Survival analysis revealed an unfavorable prognosis for patients with tumors characterized by a higher mutation burden attributed to signature 16 as well as cases in Subcluster C2. Finally, a LASSO-Cox regression model was applied to prioritize clinically relevant signatures and to establish a prognostic risk score for head and neck squamous cell carcinoma patients. In conclusion, our study provides a proof of concept that computational analysis of somatic mutational signatures is not only a powerful tool to decipher environmental and intrinsic processes in the pathogenesis of HNC, but could also pave the way to establish reliable prognostic patterns. Abbreviations: FFPE, formalin fixed paraffin embedded; HIPO, Heidelberg Center for Personalized Oncology; HNC, head and neck cancer; HNSCC, head and neck squamous cell carcinoma; HPV, human papillomavirus; TCGA, The Cancer Genome Atlas; TSS, transcription start sites.

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“…Furthermore, Ludwig et al performed comprehensive profiling of the UM-SCC oral cavity cell line panel and provided evidence of multiple clones through copy number analysis and fluorescence in situ hybridization. 17 The concept of cell line evolution in culture was highlighted more recently in a comprehensive characterization of 27 MCF7 strains in which the authors observed considerable variations in genetics, gene expression programs, morphology, and drug response. 44 Many of the cell lines discussed here have been distributed to laboratories throughout the world, and genetic drift and divergence among lineages cultured in different laboratories is highly likely.…”

Section: Discussionmentioning

confidence: 99%

“…To annotate and filter the variants of interest, the commercially available tool Goldex Helix Varseq v1.4.0 (Golden Helix, Inc., Bozeman, Montana) was used. Filters were set as previously described …”

Section: Methodsmentioning

confidence: 99%

The molecular landscape of the University of Michigan laryngeal squamous cell carcinoma cell line panel

et al. 2019

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Background Laryngeal squamous cell carcinomas (LSCCs) have a high risk of recurrence and poor prognosis. Patient‐derived cancer cell lines remain important preclinical models for advancement of new therapeutic strategies, and comprehensive characterization of these models is vital in the precision medicine era. Methods We performed exome and transcriptome sequencing as well as copy number analysis of a panel of LSCC‐derived cell lines that were established at the University of Michigan and are used in laboratories worldwide. Results We observed a complex array of alterations consistent with those reported in The Cancer Genome Atlas head and neck squamous cell carcinoma project, including aberrations in PIK3CA, EGFR, CDKN2A, TP53, and NOTCH family and FAT1 genes. A detailed analysis of FAT family genes and associated pathways showed disruptions to these genes in most cell lines. Conclusions The molecular profiles we have generated indicate that as a whole, this panel recapitulates the molecular diversity observed in patients and will serve as useful guides in selecting cell lines for preclinical modeling.

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The genomic landscape of UM-SCC oral cavity squamous cell carcinoma cell lines

Cited by 30 publications

References 44 publications

PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis

PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis

Unraveling most abundant mutational signatures in head and neck cancer

The molecular landscape of the University of Michigan laryngeal squamous cell carcinoma cell line panel

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