The transcriptional landscape analysis of basal cell carcinomas reveals novel signalling pathways and actionable targets

Litvinov, Ivan V.; Xie, Pingxing; Gunn, Scott R.; Sasseville, Denis; Lefrançois, Pascale

doi:10.26508/lsa.202000651

Cited by 14 publications

(9 citation statements)

References 63 publications

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“…This study, along with a larger pooled analysis of publicly available RNA-seq data by Litvinov et al. confirmed known dysregulated pathways in BCC and also suggested new therapeutic targets in the Wnt/β-catenin as well as IL-17 signaling pathways [ 15 , 16 ]. Other groups have used RNA-seq to elucidate the molecular underpinnings of skin malignancies.…”

Section: Recent Applications Of Rna-seq In Skin Cancermentioning

confidence: 99%

Unravelling the landscape of skin cancer through single-cell transcriptomics

Srivastava

Bencomo

Das

et al. 2023

Translational Oncology

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Section: Recent Applications Of Rna-seq In Skin Cancermentioning

confidence: 99%

Unravelling the landscape of skin cancer through single-cell transcriptomics

Srivastava

Bencomo

Das

et al. 2023

Translational Oncology

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“…3D). Platelet-derived growth factor (PDGF) and WNT/β-catenin systems may contribute to the development of basal cell carcinoma (Litvinov et al, 2021;Sellheyer, 2011). Both pathways are extracellular matrix components.…”

Section: Selection Of Ptch1 Variantsmentioning

confidence: 99%

The transcriptome analysis of cleft lip/palate-related PTCH1 variants in GMSM-K cells show carcinogenic potential

LI¹,

ZHANG²,

Huang³

et al. 2023

Biocell

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Cancer progression involves the sonic hedgehog (SHH) pathway, in which the receptor PTCH1 actives the downstream pathways. Dysfunction of PTCH1 can lead to nevoid basal cell carcinoma Syndrome (NBCCs) including neoplastic disease and congenital disorder. To evaluate the relationship between PTCH1 and cancer, we applied the CRISPR/Cas9 system to knock out PTCH1 in oral nontumorous epithelial cells (GMSM-K). Then we screened six PTCH1 variants associated with cleft lip/palate (CL/P), one of the congenital disorders in NBCCs, and generated PTCH1 variant and wild-type recombinant PTCH1 −/− GMSM-K cell lines. Transcriptome sequencing was conducted in these cell lines. The results revealed that differentially expressed genes (DEGs) in PTCH1 −/− GMSM-K were enriched in extracellular compartments, contributing epithelial diseases by pathway enrichment analysis. RT-PCR confirmed that KRT34, KRT81, KRT86, PDGFB, and WNT10B genes, associated with extracellular compartments were highly expressed in PTCH1 −/− . The Kyoto Encyclopedia of Genes and Genomes analysis also suggested that DEGs are closely related to focal adhesion, transcriptional misregulation, and proteoglycans in breast and gastric cancers. Comparative analysis of samples revealed that the CL/P-associated PTCH1 variants A443G and V908G are potentially carcinogenic. These findings provide new insights into the carcinogenic potential of PTCH1 dysfunction.

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“…Basal Cell Carcinoma (BCC) is the most common human cancer (Lefrancois et al 2020; Litvinov et al 2021). BCC driver mutations are typically found in the Sonic Hedgehog pathway genes, such as PTCH1, SMO and SUFU , and in TP53 .…”

Section: To the Editormentioning

confidence: 99%

Analysis of multiple basal cell carcinomas (BCCs) arising in one individual highlights genetic tumor heterogeneity and identifies novel driver mutations

Xie

Lefrançois

Sasseville

et al. 2022

J. Cell Commun. Signal.

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Basal cell carcinoma (BCC) is the most common human cancer, especially in individuals with light skin phototypes (i.e., Fitzpatrick I‐II skin type). Many affected develop multiple BCCs during their lifetime. It is not uncommon to observe elderly patients with >5 BCCs. In this study, we explored whether for patients diagnosed with multiple BCCs, analyzing the genomic mutations in one tumor could be sufficient to derive meaningful molecular/genetic conclusions regarding the other BCC tumors. Following the Genome Analysis Toolkit (GATK) best practices we have completed the study of 6 BCCs that occurred in an 83‐year‐old Caucasian male due to sun exposure. We have analyzed exome sequencing data of each BCC tumor and matched normal skin samples. We identified that BCCs from the same patient shared some of the key driver mutations, but they also displayed significant intertumoral heterogeneity. This finding may in part explain the different clinical progression/evolution of BCCs observed in the same patient. This work also highlights the value of characterizing multiple BCCs in one individual to identify patient‐specific genetic events with a potential link to other malignancies and implications for personalized medicine.

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The transcriptional landscape analysis of basal cell carcinomas reveals novel signalling pathways and actionable targets

Cited by 14 publications

References 63 publications

Unravelling the landscape of skin cancer through single-cell transcriptomics

Unravelling the landscape of skin cancer through single-cell transcriptomics

The transcriptome analysis of cleft lip/palate-related PTCH1 variants in GMSM-K cells show carcinogenic potential

Analysis of multiple basal cell carcinomas (BCCs) arising in one individual highlights genetic tumor heterogeneity and identifies novel driver mutations

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