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Lymph node metastasis in oral cancer is strongly associated with chromosomal instability and DNA repair defects
Author(s) -
Biswas Nidhan K.,
Das Chitrarpita,
Das Subrata,
Maitra Arindam,
Nair Sudhir,
Gupta Tejpal,
D'Cruz Anil K.,
Sarin Rajiv,
Majumder Partha P.
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32305
Subject(s) - genome instability , biology , exome , dna repair , cancer research , homologous recombination , chromosome instability , germline , germline mutation , metastasis , somatic cell , cancer , exome sequencing , genetics , gene , mutation , dna , dna damage , chromosome
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.