Germline mutation in the TP53 gene in uveal melanoma

Scientific Reports
Nikola HajkovaIvana Ticha

Abstract

We performed comprehensive molecular analysis of five cases of metastasizing uveal malignant melanoma (UM) (fresh-frozen samples) with an NGS panel of 73 genes. A likely pathogenic germline TP53 mutation c.760A > G (p.I254V) was found in two tumor samples and matched nontumor tissue. In three cases, pathogenic BAP1 mutation was detected together with germline missense variants of uncertain significance in ATM. All cases carried recurrent activating GNAQ or GNA11 mutation. Moreover, we analyzed samples from another 16 patients with primary UM by direct Sanger sequencing focusing only on TP53 coding region. No other germline TP53 mutation was detected in these samples. Germline TP53 mutation, usually associated with Li-Fraumeni syndrome, is a rare event in UM. To the best of our knowledge, only one family with germline TP53 mutation has previously been described. In our study, we detected TP53 mutation in two patients without known family relationship. The identification of germline aberrations in TP53 or BAP1 is important to identify patients with Li-Fraumeni syndrome or BAP1 cancer syndrome, which is also crucial for proper genetic counseling.

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Citations

May 31, 2020·Nature Reviews. Cancer·Michele CarboneHaining Yang
Apr 7, 2020·Journal of Cutaneous Pathology·Atrin ToussiMaija Kiuru
Jan 6, 2021·International Journal of Molecular Sciences·Natasha M van PoppelenEmine Kiliҫ
Aug 2, 2019·Ocular Oncology and Pathology·Christopher B ToomeyJonathan H Lin
Dec 23, 2021·Experimental and Therapeutic Medicine·Florica SandruAdina Ghemigian

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Software Mentioned

SiPhy
HDIV
Polyphen2
MutationTaster
MutationAssessor
HVAR
phyloP46
Pindel
PROVEAN GERP + +
NextGENe®

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