DNA Double-Strand Break Repair by Non-homologous End Joining and Its Clinical Relevance - DNA Repair in Cancer Therapy - page 176

TABLE 8.2 NHEJ Gene Expression or Protein Levels as Potential Prognostic or Predictive Markers

Malignancy Genes/proteins Analysis Comments Reference

Non-small cell lung
cancer

ATM, Ku80, DNA-PKcs Comparison of tumor:normal tissue

expression by RT-PCR of mRNA

Prognostic:
Patients with high tumor:normal expression ratios of ATM or
DNA-PKcs , but not Ku80 , had shorter median survival than
patients with low ratios

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Non-small cell lung
cancer

Ku70 , Ku80 , XRCC4 , LIG4 SNP analysis of DNA taken from

peripheral blood lymphocytes

Prognostic:
A SNP in XRCC4 that potentially abolishes an acceptor splice
site at exon 8 was strongly associated with poorer survival

231

Ku70 , Ku80 Prognostic:

Low expression of Ku70 and Ku80 at transcriptional and
translational levels were strongly associated with advanced
high grade and high stage TCC

Transitional cell
carcinoma of the
bladder (TCC)

RT-PCR of mRNA and
immunohistochemistry

317

Head and neck cancer Ku70 , Ku80 , DNA-PKcs RT-PCR of mRNA in pretreatment

tumors and immunohistochemistry of
patients receiving chemoradiotherapy
or radiotherapy after induction
chemotherapy

Predictive:
High tumor expression of all three genes, especially Ku70 ,
was associated with response to induction chemotherapy.
High expression of Ku70 protein significantly related to local
recurrence-free survival and the percentage of Ku70 positive
cells in the tumor was associated with overall patient
survival

258

Breast cancer ATM RT-PCR of mRNA from tumor and

adjacent normal tissue

Prognostic:
High ATM expression in tumor tissue was associated with
a more favorable overall survival

318

Early breast cancer ATM, Mre11, Rad50, Nbs1 Immunohistochemistry of tumors

from women randomized to receive
postoperative radiotherapy or
adjuvant chemotherapy

Predictive:
High expression of MRN complex was associated with
increased local recurrence-free survival

257

Acute myeloid
leukemia

ATM , NBS1 , RAD50 , Ku80
and 11 other genes

SNP analysis of DNA from patients
and controls

Predictive:
Patients heterozygous for a SNP in the ATM gene (4138C

319

> T)

were linked to inferior short-term response rate and
long-term survival

Mre11 , Ku80 , XRCC4 , and
24 other non-NHEJ DNA
repair genes

Prognostic:
Expression of 13 genes including Ku80 and XRCC4 was
reduced in grade II, III and IV astrocytomas. Mre11
expression was significantly reduced in grade III and IV
tumors. Decreased expression of eight genes, including
Mre11 , Ku80 and XRCC4 , was associated with poor overall
survival

Astrocytoma mRNA expression in tumor and

normal tissue probed by TaqMan
low-density array

320

Advanced gastric
cancer

ATM phosphorylation Immunohistochemistry Prognostic:

Low-level ATM phosphorylation was significantly
associated with lymph node metastasis and poor 5-year
survival

321