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TP53功能增益突变是高甲基化转移性结肠直肠癌的不良预后因素

Shonosuke Wakayama¹, Kota Ouchi¹, Shin Takahashi¹

¹Department of Medical Oncology, Tohoku University Hospital, Sendai, Miyagi, Japan; Department of Clinical Oncology, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan.

Clinical colorectal cancer

|June 24, 2023

概括

转移性结直肠癌患者具有高甲基化结直肠癌 (HMCC) 和TP53功能增益 (GOF) 突变,面临最差的生存结果. 这种组合的分子形状确定了一个关键的子组,需要有针对性的治疗策略.

科学领域:

在瘤学瘤学.
遗传学是一个遗传学.
分子生物学分子生物学

背景情况:

TP53突变和DNA甲基化并不是转移性结直肠癌 (mCRC) 的确立生物标志物.
分析结合TP53突变功能亚型和全基因组DNA甲基化状态 (GWMS) 可能会提高mCRC的预后准确性.

研究的目的:

在转移性结直肠癌患者中调查结合TP53突变功能亚型和GWMS的预后价值.

主要方法:

利用了来自TRICOLOREIII期试验的临床数据.
将TP53突变分为野生类型,功能增益型 (GOF) 和非功能增益型 (非GOF).
根据GWMS,将瘤分类为高甲基化结直肠癌 (HMCC) 和低甲基化结直肠癌 (LMCC).

主要成果:

高甲基化结直肠癌 (HMCC) 患者的整体存活期 (OS) 比低甲基化结直肠癌 (LMCC) 患者要短 (25.3个月与40.3个月).
与其他组合的子组相比,HMCC/GOF子组表现出明显较短的OS (17.7个月).
高甲基化结直肠癌 (HMCC) 被通过多变量分析确定为TP53GOF突变组的预后不良因素.

结论:

TP53 GOF突变和高甲基化结直肠癌 (HMCC) 的组合定义了转移性结直肠癌中新的,预后最差的分子子集.
这一发现强调了评估TP53突变状态和DNA甲基化对于mCRC精确预后的重要性.

关键词:

通过DNA甲基化.这种突变是TP53突变.

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