Presentation Exploration of mechanisms for chromothripsis by irradiation.

Morishita, Maki  ,  Muramatsu, Tomoki  ,  Hayashi, Shin  ,  Hirai, Momoki  ,  Suto, Yumiko  ,  Konishi, Teruaki  ,  Moriyama, Keiji  ,  Inazawa, Johji

Chromothripsis is the massive but highly localized chromosome rearrangements within a one-step catastrophic event rather than a series of subsequent and random alterations. Chromothripsis occurs commonly in various human cancers and it is thought to be associated with increasing malignancy and oncogenesis. However the causes and consequences of chromothripsis remain unclear. Therefore, to explore mechanisms of chromothripsis, we investigated whetherchromothripsis was artificially induced by irradiation. We elicited DNA double-strand breaks in the oral cancer cell line HOC313, or its highly metastatic subline HOC313-LM by The Single Particle Irradiation system to Cell (SPICE), a focused vertical micro-beam system designed to irradiate the nuclei of adhesive cells. We established irradiated monoclonal sublines and analyzed the copy number variations (CNVs) and SNPs using SNP array. Chromosomal alterations, induced by irradiation including CNVs, were detected in some monoclonal sublines. Interestingly SNP array analysis showed that onesubline named LM200-#25 had multiple chromosomal alterations which happened locally in chromosome 7. Moreover, we detected several chromosomal alterations such as t(12;7;11) translocation in LM200-#25 subline by Multi-Color FISH analysis. These results suggested that chromothripsis might be induced by irradiation in LM200-#25 subline.
American Association for Cancer Research Annual Meeting 2015

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