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Changes in the genetic landscape during the malignization of high grade squamous intraepithelial lesion into cervical cancer.
- Source :
-
Current problems in cancer [Curr Probl Cancer] 2020 Oct; Vol. 44 (5), pp. 100567. Date of Electronic Publication: 2020 Mar 17. - Publication Year :
- 2020
-
Abstract
- In 5 patients, a change in the genetic landscape from HPV16 positive high-grade squamous intraepithelial lesion (HSIL) to squamous cervical cancer was traced, which occurred in these patients within the period from 7 months to 5 years after diagnosing HSIL.<br />Materials and Methods: The DNA from paraffin blocks of dysplasia tissue and the tumor that emerged afterwards was used for the study, which was analyzed using the OncoScan FFPE microarray Assay Kit Affymetrix (USA) for genome-wide determination of gene abundance and 65 key somatic driver mutations of oncogenes and tumor suppressor genes.<br />Results: In the study of HSIL material, somatic mutations were observed in 4/5 cases, 18 different somatic driver mutations of the NRAS, EGFR, BRAF, KRAS, IDH2 oncogenes and TP53 suppressor genes were found and almost no CNA-Copy Number Aberration was identified. HSIL malignization is associated with the appearance of secondary driver mutations in oncogenes and tumor suppressor genes and a large number of structural and numerical CNA, the frequency of which correlates with the time of dysplasia malignization into cancer with a very high correlation coefficient r = 0.98, P = 0.004. The trees of dysplasia evolution into tumor were constructed for each patient.<br />Conclusion: According to the results of the work, it is assumed that the initiation of the development of mucosa dysplastic changes is due to primary driver mutations. The formation of secondary driver mutations and CNA are genetic mechanisms of malignant transformation, while the scenarios of the evolution of dysplasia into a tumor are individual and very diverse.<br /> (Copyright © 2020. Published by Elsevier Inc.)
- Subjects :
- Female
Follow-Up Studies
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Papillomavirus Infections virology
Prognosis
Squamous Intraepithelial Lesions genetics
Squamous Intraepithelial Lesions virology
Survival Rate
Uterine Cervical Neoplasms genetics
Uterine Cervical Neoplasms virology
Uterine Cervical Dysplasia genetics
Uterine Cervical Dysplasia virology
Biomarkers, Tumor genetics
Mutation
Papillomaviridae isolation & purification
Papillomavirus Infections complications
Squamous Intraepithelial Lesions pathology
Uterine Cervical Neoplasms pathology
Uterine Cervical Dysplasia pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1535-6345
- Volume :
- 44
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Current problems in cancer
- Publication Type :
- Academic Journal
- Accession number :
- 32201051
- Full Text :
- https://doi.org/10.1016/j.currproblcancer.2020.100567