ESTRO meets Asia 2024 - Abstract Book

S50

Interdisciplinary – Biomarkers

ESTRO meets Asia 2024

and FANCM), and group of MSH genes (MSH2, MSH3, MSH4 and MSH6). 4 A correlation of the subjects’ phenotype was done with the mutational information on those key DNA repair genes.

Results:

All those three samples with locally advanced stage III and IVA nasopharyngeal cancer were treated with induction chemotherapy followed by chemoradiation. Two samples did not have any structural variants in all assessed key DNA repair genes and perform very well after treatment. Both patients had complete locoregional response. One sample with structural variants in almost all key DNA repair genes did poorly (see Table 1), only partial response after treatment. Furthermore, 2 months after treatment, that poor responder patient developed lung metastasis. It is likely that defective DNA repair genes in the poor responder associated with more aggressive cancer phenotype and less response to standard treatment. The defective DNA repair genes were not just associated with increased propensity to metastasis, but also resulting in more resilient tumour toward DNA damaging agents including radiation therapy and chemotherapy. 5

Table 1: Structural variants in non-intergenic and non-intron regions from 3 nasopharyngeal samples

Genes

Sample Partial Responder

Complete Responder

Complete Responder

ATM

1

0

0

BRCA1

1

0

0

BRCA2

0

0

0

CDK12

1

0

0

CHEK2

0

0

0

PALB2

1

0

0

POLE

1

0

0

RAD51B

20

0 0

0 0

TP53

0

FANC group

gene

9

0

0

MSH

gene

1

0

0

group

Conclusion:

DNA repair genes are necessary to maintain DNA replication error or DNA repair errors. Large structural variants in DNA repair genes translate into more aggressive tumour and more resistant to standard treatment in nasopharyngeal cancer. The underlying mechanism of such phenomenon is worthy to be explored in further basic studies. The assessment of DNA repair genes can also be prognostic clinically and need to assess in prospective clinical trials.

Keywords: DNA repair, structural variations, NPC

References:

1. Smolka, M. et al. Detection of mosaic and population-level structural variants with Sniffles2. Nat. Biotechnol. (2024) doi:10.1038/s41587-023-02024-y.