Dataset Information

Utility of CYP2D6 copy number variants as prognostic biomarker in localized anal squamous cell carcinoma

ABSTRACT: Anal squamous cell carcinoma (ASCC) is an infrequent tumor. Since 70s, treatment of stages II-III consists on a combination of 5-fluorouracil (5FU), mitomycin C (MMC), and radiotherapy. The aim of this study is the identification of biomarkers that allow personalized treatment and improvement of therapeutic outcomes. Forty-six tumor paraffin samples from ASCC patients were analyzed by whole-exome sequencing. Single nucleotide polymorphisms and copy number variants (CNVs) were identified and their relation to disease-free survival (DFS) was studied using BRB Array Tool and Kaplan-Meier analyses. Obtained findings were validated in an independent retrospective cohort of 101 ASCC patients with stages I-III from eleven hospitals within the Multidisciplinary Spanish Digestive Cancer Group (GEMCAD) using qPCR Copy Number Assays. GEMCAD validation cohort was also analyzed using mass spectrometry proteomics to assess the biological features of these tumors.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Anal Canal

DISEASE(S): Anal Canal Squamous Cell Carcinoma

SUBMITTER: Antje Dittmann

LAB HEAD: Jaime Feliu

PROVIDER: PXD037816 | Pride | 2023-04-26

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	20220125_002_S346604_11_rep.raw	Raw
	20220125_003_S346671_78.raw	Raw
	20220125_004_S346624_31.raw	Raw
	20220125_005_S346627_34.raw	Raw
	20220125_007_S346645_52.raw	Raw

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Publications

Utility of CYP2D6 copy number variants as prognostic biomarker in localized anal squamous cell carcinoma.

Trilla-Fuertes Lucía L Gámez-Pozo Angelo A Nogué Miguel M Busquier Isabel I Arias Fernando F López-Campos Fernando F Fernández-Montes Ana A Ruiz Ana A Velázquez Concepción C Martín-Bravo Celia C Pérez-Ruiz Elisabeth E Asensio Elena E Hernández-Yagüe Xavier X Rodrigues Aline A Ghanem Ismael I López-Vacas Rocío R Hafez Ahmed A Arias Pedro P Dapía Irene I Solís Mario M Dittmann Antje A Ramos Ricardo R Llorens Carlos C Maurel Joan J Campos-Barros Ángel Á Fresno Vara Juan Ángel JÁ Feliu Jaime J

Cancer 20230425 16

<h4>Background</h4>Anal squamous cell carcinoma (ASCC) is an infrequent tumor whose treatment has not changed since the 1970s. The aim of this study is the identification of biomarkers allowing personalized treatments and improvement of therapeutic outcomes.<h4>Methods</h4>Forty-six paraffin tumor samples from ASCC patients were analyzed by whole-exome sequencing. Copy number variants (CNVs) were identified and their relation to disease-free survival (DFS) was studied and validated in an indepen ...[more]

PMID: 37096763

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Project description:Gene copy-number variation, which provides the raw material for the evolution of novel genes, is surprisingly widespread in natural populations. Experimental evolution studies have demonstrated an extremely high spontaneous rate of origin of gene duplications. When organisms are suboptimally adapted to their environment, gene duplication may compensate for reduced fitness by amplifying promiscuous activity of a gene, or increasing dosage of a suboptimal gene. The overarching goal of this study is to inverstigate whether CNVs constitute a common mechanism of adaptive genetic change during compensatory evolution and to further characterize the role of natural selection in dictating their evolutionary spread at a population-genomic level. Outcrossing populations of C. elegans with low fitness were evolved for >200 generations and the frequencies of CNVs in these populations were analyzed by oligonucleotide array comparative genome hybridization, quantitative PCR, and single-worm PCR. Multiple duplications and deletions were detected in intermediate to high frequencies and several lines of evidence suggest that the changes in frequency were adaptive. 1) Many copy-number changes reached high frequency, were near fixation, or were fixed in a short time. 2) Many independent duplications and deletions in high frequency harbor overlapping regions which likely include genes that are under selection for either higher or lower rates of expression. 3) The size spectrum of deuplications and deletions in the adaptive recovery populations is significantly larger than that of spontaneous copy-number variants in mutation accumulation experiments. This is expected if larger CNVs are more likely to encompass genes that are being selected for altered gene dosage. Out results validate the great potential borne by gene copy-number changes for compensatory evolution and adaptation. Experimental genome evolution of copy-number variants in 25 experimental lines compared to 5 ancestral control lines.