Nature子刊:全基因组测序深度挖掘转移性大肠癌的分子图谱
创作:花开 审核:爱的抉择 04月03日
  • 429例转移性结直肠癌(mCRC)在开始新的全身性治疗前完成活检,进行全基因组测序;
  • 利用基因组的突变特征可将病人分成3组,原发CRC特征组、既往治疗相关特征组和转移特异性特征组;
  • 与原发CRC相比,新鉴定出一些(非编码)驱动基因,其突变频率增加,并鉴定出一些易于被微卫星不稳定性影响的特定基因;
  • CRC特定的1Kb-10Mb缺失在常见的脆弱位点富集,LINC00672突变通常与治疗反应有关,FBXW7突变与EGFR靶向治疗的疗效较差有关。
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爱的抉择
Nature Communications近期发表的文章,通过对429名转移性结直肠癌(mCRC)患者的活检样本进行全基因组测序,发现mCRC的基因组图谱与原发性CRC具有明显的变化,其受到既往治疗的影响,同时包含与临床治疗相关的特征,或可有助于对mCRC患者的精准医疗。
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Whole genome sequencing of metastatic colorectal cancer reveals prior treatment effects and specific metastasis features

转移性结直肠癌的全基因组测序揭示既往治疗的疗效与特异性转移特征

10.1038/s41467-020-20887-6

01-25, Article

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Abstract:收起
In contrast to primary colorectal cancer (CRC) little is known about the genomic landscape of metastasized CRC. Here we present whole genome sequencing data of metastases of 429 CRC patients participating in the pan-cancer CPCT-02 study (NCT01855477). Unsupervised clustering using mutational signature patterns highlights three major patient groups characterized by signatures known from primary CRC, signatures associated with received prior treatments, and metastasis-specific signatures. Compared to primary CRC, we identify additional putative (non-coding) driver genes and increased frequencies in driver gene mutations. In addition, we identify specific genes preferentially affected by microsatellite instability. CRC-specific 1kb-10Mb deletions, enriched for common fragile sites, and LINC00672 mutations are associated with response to treatment in general, whereas FBXW7 mutations predict poor response specifically to EGFR-targeted treatment. In conclusion, the genomic landscape of mCRC shows defined changes compared to primary CRC, is affected by prior treatments and contains features with potential clinical relevance.

First Authors:
Pauline A J Mendelaar,Marcel Smid

Correspondence Authors:
Saskia M Wilting

All Authors:
Pauline A J Mendelaar,Marcel Smid,Job van Riet,Lindsay Angus,Mariette Labots,Neeltje Steeghs,Mathijs P Hendriks,Geert A Cirkel,Johan M van Rooijen,Albert J ten Tije,Martijn P Lolkema,Edwin Cuppen,Stefan Sleijfer,John W M Martens,Saskia M Wilting

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