基因组不稳定性
生物
外显子组
DNA修复
癌症研究
同源重组
染色体不稳定性
生殖系
种系突变
转移
体细胞
癌症
外显子组测序
遗传学
基因
突变
DNA
DNA损伤
染色体
作者
Nidhan K. Biswas,Chitrarpita Das,Subrata Das,Arindam Maitra,Sudhir Nair,Tejpal Gupta,Anil D’Cruz,Rajiv Sarin,Partha P. Majumder
摘要
Oral squamous cell carcinoma (OSCC) is highly prevalent in south and southeast Asia. Many (30–50%) OSCC patients develop lymph node metastasis (LNM), which is the most important prognostic factor in OSCC. To identify genomic correlates of LNM, we compared exome sequences and copy number variation data of blood and tumor DNA from highly contrasting subgroups of patients to reduce false inferences—( i ) patients with LNM and ( ii ) patients with late stage disease but without LNM. We found that LNM is associated with ( i ) specific hotspot somatic mutations in TP53 and CASP8 ; ( ii ) rare nonsilent germline mutations in BRCA2 and FAT1 ; ( iii ) mutations in mito‐G2/M and nonhomologous end joining (NHEJ) pathways; ( iv ) recurrent deletion of genes for DNA repair by homologous recombination; and ( v ) chromosomal instability. LN+ patients with NHEJ pathway mutations have longer disease‐free survival. Five genomic features have a high predictive value of LNM.
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