High-risk follicular lymphomas harbour more somatic mutations including those in the AID-motif View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Taku Tsukamoto, Masakazu Nakano, Ryuichi Sato, Hiroko Adachi, Miki Kiyota, Eri Kawata, Nobuhiko Uoshima, Satoru Yasukawa, Yoshiaki Chinen, Shinsuke Mizutani, Yuji Shimura, Tsutomu Kobayashi, Shigeo Horiike, Akio Yanagisawa, Masafumi Taniwaki, Kei Tashiro, Junya Kuroda

ABSTRACT

We investigated clinical and genetic characteristics of high-risk follicular lymphoma (FL), that lacked evidence of large cell transformation at diagnosis, in the rituximab era. First, we retrospectively analysed the clinical features of 100 patients with non-transformed FL that were consecutively treated with rituximab-containing therapies in a discovery cohort. The presence of either peripheral blood and/or bone involvement was associated with short progression-free survival. This was confirmed in a validation cohort of 66 FL patients. Then, whole exome sequencing was performed on randomly selected 5 high- and 9 standard-risk FL tumours. The most common mutational signature was a CG > TG substitution-enriched signature associated with spontaneous deamination of 5-methylcytosine at CpG, but mutations in WA and WRC(Y) motifs (so-called activation-induced cytidine deaminase (AID) motifs) were also enriched throughout the whole exome. We found clustered mutations in target sequences of AID in the IG and BCL2 loci. Importantly, high-risk FLs harboured more somatic mutations (mean 190 vs. 138, P = 0.04), including mutations in WA (33 vs. 22, P = 0.038), WRC (34 vs. 22, P = 0.016) and WRCY motifs (17 vs. 11, P = 0.004). These results suggest that genomic instability that allows for emergence of distinct mutations through AID activity underlies development of the high-risk FL phenotype. More... »

PAGES

14039

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-017-14150-0

    DOI

    http://dx.doi.org/10.1038/s41598-017-14150-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1092297805

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29070849


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