CDKN2A/B Homozygous Deletions in Astrocytomas: A Literature Review

• Published in: Current issues in molecular biology 2023-06, Vol.45 (7), p.5276-5292
• Main Authors: Yuile, Alexander, Satgunaseelan, Laveniya, Wei, Joe Q, Rodriguez, Michael, Back, Michael, Pavlakis, Nick, Hudson, Amanda, Kastelan, Marina, Wheeler, Helen R, Lee, Adrian
• Format: Article
• Language: English
• Subjects: CDKN2A/B alterations; CDKN2A/B heterozygous deletions; CDKN2A/B homozygous deletions; grade 4 astrocytomas; IDH mutant glioblastomas; radiotherapy; Review
• ISSN: 1467-3045; 1467-3037; 1467-3045
• DOI: 10.3390/cimb45070335

Genomic alterations of and in astrocytomas have been an evolving area of study for decades. Most recently, there has been considerable interest in the effect of and/or ( ) homozygous deletions (HD) on the prognosis of ( )-mutant astrocytomas. This is highlighted by the adoption of HD as an essential criterion for astrocytoma and -mutant central nervous system (CNS) WHO grade 4 in the fifth edition of the World Health Organisation (WHO) Classification of Central Nervous System Tumours (2021). The and genes are located on the short arm of chromosome 9. encodes for two proteins, p14 and p16, and encodes for p15. These proteins regulate cell growth and angiogenesis. Interpreting the impact of alterations on astrocytoma prognosis is complicated by recent changes in tumour classification and a lack of uniform standards for testing . While the prognostic impact of HD is established, the role of different alterations-heterozygous deletions (HeD), point mutations, and promoter methylation-is less clear. Consequently, how these alternations should be incorporated into patient management remains controversial. To this end, we reviewed the literature on different alterations in -mutant astrocytomas and their impact on diagnosis and management. We also provided a historical review of the changing impact of alterations as glioma classification has evolved over time. Through this historical context, we demonstrate that HD is an important negative prognostic marker in -mutant astrocytomas; however, the historical data is challenging to interpret given changes in tumour classification over time, variation in the quality of evidence, and variations in the techniques used to identify deletions. Therefore, future prospective studies using uniform classification and detection techniques are required to improve the clinical interpretation of this molecular marker.