Preview

Advances in Molecular Oncology

Advanced search

Comprehensive analysis of chromosome 8 abnormalities and its prognostic value in patients with uveal melanoma

https://doi.org/10.17650/2313-805X-2022-9-1-57-63

Abstract

Introduction. Uveal melanoma ability to metastasize depends on a few prognostic factors. The genetic ones are considered to be the most significant. The role of disorders of the short arm of chromosome 8 (8p), as well as a combination of changes in 8p and the long arm of this chromosome (8q) in the development of metastatic lesions in this pathology remains insufficiently studied.
The study objective – to evaluate the prognostic value of chromosome 8 abnormalities in patients with uveal melanoma.
Materials and methods. We analyzed 2 retrospective groups of patients who underwent enucleation for uveal melanoma, statistically homogeneous in the main clinical parameters. Group 1 included patients without signs of metastases (n = 41) with an average follow-up period of 71 months, Group 2 included patients with detected metastases (n = 51) and an average follow-up period of 21 months Chromosome abnormalities were tested by multiplex ligation-dependent probe amplification.
Results. Three- and five-year survival in patients with uveal melanoma without 8p deletion were 64 and 54 %, respectively; with 8p deletion significantly lower – 25 and 6 %, respectively. The same survival rates in patients with uveal melanoma with 8q amplification were 43 and 26 %, respectively, whereas in patients without 8q amplification they were significantly higher – 80 and 74 %, respectively. In patients with uveal melanoma harbouring both abnormalities, 3- and 5-year survival rates were 26 and 7 %, whereas isolated 8q amplification was associated with 47 and 35 % survival, respectively. These survival rates differ greatly and significantly: hazard ratio 3,26 (95 % confidence interval 1,86–5,69) and 6,89 (95 % confidence interval 2,67–17,73), respectively (р <0,0001).
Conclusion. The findings support comprehensive evaluation of chromosome 8 abnormalities as a substantial part of uveal melanoma prognostication. 8q amplification, 8p deletion, combination of these abnormalities and its role in uveal melanoma malignity should be further discovered. Further research in this direction is needed.

About the Authors

V. A. Yarovaya
S.N. Fedorov MNTC «Eye Microsurgery», Ministry of Health of Russia
Russian Federation

Vera Andreevna Yarovaya 

59 Beskudnikovsky Bul’var, Moscow127486



A. A. Yarovoy
S.N. Fedorov MNTC «Eye Microsurgery», Ministry of Health of Russia
Russian Federation

59 Beskudnikovsky Bul’var, Moscow127486



L. V. Chudakova
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation

1 Ostrovityanova St., Moscow 117997



I. A. Levashov
S.N. Fedorov MNTC «Eye Microsurgery», Ministry of Health of Russia
Russian Federation

59 Beskudnikovsky Bul’var, Moscow127486



A. R. Zaretskiy
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation

1 Ostrovityanova St., Moscow 117997



References

1. Onken M.D., Worley L.A., Char D.H. et al. Collaborative Ocular Oncology Group Report Number 1: prospective validation of a multi-gene prognostic assay in uveal melanoma. Ophthalmology 2012;119(8):1596–603. DOI: 10.1016/j.ophtha.2012.02.017.

2. Singh A.D., Zabor E.C., Radivoyevitch T. Estimating cured fractions of uveal melanoma. JAMA Ophthalmol 2021;139(2):174– 81. DOI: 10.1001/jamaophthalmol.2020.5720.

3. Jager M.J., Shields C.L., Cebulla C.M. et al. Uveal melanoma. Nat Rev Dis Primers 2020;6(1):24. DOI: 10.1038/s41572-020-0158-0.

4. Mazloumi M., Vichitvejpaisal P., Dalvin L.A. et al. Accuracy of The Cancer Genome Atlas Classification vs american joint committee on cancer classification for prediction of metastasis in patients with uveal melanoma. JAMA Ophthalmol 2020;138(3):260–7. DOI: 10.1001/jamaophthalmol.2019.5710.

5. Jager M.J., Brouwer N.J., Esmaeli B. The Cancer Genome Atlas Project: an integrated molecular view of uveal melanoma. Ophthalmology 2018;125(8):1139–42. DOI: 10.1016/j.ophtha.2018.03.011.

6. Dogrusöz M., Jager M.J. Genetic prognostication in uveal melanoma. Acta Ophthalmol 2018;96(4):331–47. DOI: 10.1111/aos.13580.

7. Royer-Bertrand B., Torsello M., Rimoldi D. et al. Comprehensive genetic landscape of uveal melanoma by whole genome sequencing. Am J Hum Genet 2016;99(5):1190–8. DOI: 10.1016/j.ajhg.2016.09.008.

8. Shields C.L., Ganguly A., Bianciotto C.G. et al. Prognosis of uveal melanoma in 500 cases using genetic testing of fineneedle aspiration biopsy specimens. Ophthalmology 2011;118(2):396–401. DOI: 10.1016/j.ophtha.2010.05.023.

9. Robertson A.G., Shih J., Yau C. et al. Integrative analysis identifies four molecular and clinical subsets in uveal melanoma. Cancer Cell 2017;32(2):204– 20.e15. DOI: 10.1016/j.ccell.2017.07.003.

10. Damato B., Duke C., Coupland S.E. et al. Cytogenetics of uveal melanoma. Ophthalmology 2007;114(10):1925–31. DOI: 10.1016/j.ophtha.2007.06.012.

11. Shields C.L., Say E.A.T., Hasanreisoglu M. et al. Cytogenetic abnormalities in uveal melanoma based on tumor features and size in 1059 patients. Ophthalmology 2017;124(5):609–18. DOI: 10.1016/j.ophtha.2016.12.026.

12. Vichitvejpaisal P., Dalvin L.A., Mazloumi M. et al. Genetic analysis of uveal melanoma in 658 patients using the cancer genome atlas classification of uveal melanoma as A, B, C, and D. Ophthalmology 2019;126(10):1445–53. DOI: 10.1016/j.ophtha.2019.04.027.

13. Shields C.L., Say E.A.T., Hasanreisoglu M. et al. Personalized prognosis of uveal melanoma based on cytogenetic profile in 1059 patients over an 8-year period. Ophthalmology 2017;124(10):1523–31. DOI: 10.1016/j.ophtha.2017.04.003.

14. Ewens K.G., Kanetsky P.A., RichardsYutz J. et al. Genomic profile of 320 uveal melanoma cases: chromosome 8p-loss and metastatic outcome. Investigative Opthalmology & Visual Science 2013;54(8):5721–9. DOI: 10.1167/iovs.13-12195.


Review

For citations:


Yarovaya V.A., Yarovoy A.A., Chudakova L.V., Levashov I.A., Zaretskiy A.R. Comprehensive analysis of chromosome 8 abnormalities and its prognostic value in patients with uveal melanoma. Advances in Molecular Oncology. 2022;9(1):57-63. (In Russ.) https://doi.org/10.17650/2313-805X-2022-9-1-57-63

Views: 448


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2313-805X (Print)
ISSN 2413-3787 (Online)