A DNA damage response-like phenotype defines a third of colon cancers at onset. Supplementary data.

These are supplemental data to the manuscript entitled: A DNA damage response-like phenotype defines a novel subset of colon cancer. A third of de-novo presentations of colorectal cancer display foci of positivity for ℽH2AX, pCHK2, pNBS1 in the absence of apoptosis or senescence associated p21/CDKN1A. This phenotype is reminiscent of an ongoing DNA damage response (DDR). The TP53 status, the chromosome 20q amplification or the microsatellite instability gene status did not correlate with the DDR phenotype, except for a preferential association with MSH2/MSH6 inactivation and conserved MLH1. Additional lesions of DDR-associated genes may be responsible for this phenotype, which is absent from the remaining cases in this cohort. The outcome, after adjuvant treatment with DNA-damaging drugs, did not differentiate this group from the remaining cases. DDR+ colorectal cancers may be amenable to personalized therapy by targeting the DDR.本数据为题为《类似DNA损伤应答表型定义结直肠癌新亚型》的手稿的补充数据。三分之一的新发结直肠癌病例可检测到γH2AX、pCHK2、pNBS1阳性病灶，且未伴随细胞凋亡或衰老相关的p21/CDKN1A表达。该表型与活跃进行中的DNA损伤应答（DNA Damage Response, DDR）过程高度相似。TP53状态、20号染色体长臂扩增或微卫星不稳定基因状态均与该DDR表型无显著关联，仅其与MSH2/MSH6失活存在偏好性关联，且MLH1表达保持保守。DDR相关基因的额外突变可能是该表型的成因，本队列其余病例均未出现该表型。接受DNA损伤类药物辅助治疗后，该组患者的预后与其余病例并无显著差异。DDR阳性结直肠癌或可通过靶向DDR通路实现个性化治疗。