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ERCC1

MIM.126380 19q13.2-q13.3 HGNC:3433 Entrez:2067 ENSG00000012061

Sunday 5 March 2006

Definition: The heterodimer ERCC1-XPF is one of two endonucleases required for NER.

Nucleotide excision repair (NER system) is a genome caretaker mechanism responsible for removing helix-distorting DNA lesions, most notably ultraviolet photodimers. Inherited defects in NER result in profound photosensitivity and the cancer-prone syndrome xeroderma pigmentosum (XP) or two progeroid syndromes: Cockayne syndrome and trichothiodystrophy syndrome.

Pathology

- Mutations in ERCC1 have been reported in (cerebrooculofacioskeletal syndrome 4) (cerebro-oculo-facio-skeletal syndrome 4) (COFS4). (17273966)

- Mutations in XPF are associated with mild XP and rarely with progeria.

- germline mutations in ERCC1

  • cerebrooculofacioskeletal syndrome 4 (cerebro-oculo-facio-skeletal syndrome 4) (COFS4) (17273966)

- ERCC1 expression in tumors

  • ERCC1 (excision repair cross-complementing 1) expression in pT2 gallbladder cancer is a prognostic factor. (21117025).
  • ERCC1 (excision repair cross-complementation group 1) expression is a predictor for response of neoadjuvant chemotherapy for FIGO stage 2B uterine cervix cancer. (21093896).
  • Excision repair cross-complementation group 1 (ERCC1) expression in advanced urothelial carcinoma patients receiving cisplatin-based chemotherapy. (21091775).
  • No evidence of an association of ERCC1 and ERCC2 polymorphisms with clinical outcomes of platinum-based chemotherapies in non-small cell lung cancer. (21075476).
  • ERCC1 (excision repair cross-complementation group 1) expression as a predictor for response of neoadjuvant chemotherapy for FIGO stage 2B uterine cervix cancer. (21093896)

- Excision repair cross-complementing 1-118 single nucleotide polymorphisms (SNPs) have been reported as predictive markers of response to platinum-based chemotherapy. (20736746)

IHC biomarker

- ERCC1 is a Prognostic and Predictive Biomarker for Urothelial Carcinoma of the Bladder following Radical Cystectomy. (26162296)

- Predictive Role of ERCC1 Expression in Head and Neck Squamous Cell Carcinoma Patients Treated with Surgery and Adjuvant Cisplatin-Based Chemoradiation. (26066774)

- Development and Validation of an ERCC1 Immunohistochemistry Assay for Solid Tumors doi : 0.5858/arpa.2016-0006-OA

Platinum-based therapies, such as cisplatin, carboplatin, and oxaliplatin, are standard chemotherapeutic agents that are used to treat different tumor types, including non–small cell lung cancer (NSCLC), head and neck cancer, gastric cancer, bladder cancer, and colorectal cancer, among others.

Platinum compounds react with DNA to form adducts. These adducts consist of platinum-DNA monoadducts, intrastrand and interstrand cross-links, and/or DNA-protein cross-links. These DNA lesions can be repaired by the nucleotide excision repair pathway.

Within the nucleotide excision repair pathway, the excision repair cross-complementing group 1 protein (ERCC1) has a critical and rate-limiting role of recognizing and helping remove DNA adducts.

Specifically, ERCC1 forms a heterodimer with ERCC4 (previously XPF) and incises the 5′ strand of damaged DNA.

Four isoforms of the ERCC1 protein (201, 202, 203, and 204) are generated by alternative splicing of the ERCC1 gene.6 Mutations in the 201 and 203 isoforms disrupt the ERCC1 capacity in the nucleotide excision repair pathway, suggesting that these are the isoforms responsible for DNA repair.

As a biomarker, ERCC1 expression in tumors assessed by immunohistochemistry (IHC), Western blot, and reverse transcription-polymerase chain reaction is potentially predictive of response to platinum-based adjuvant chemotherapy in a variety of cancers, including lung and ovarian cancer.

Many studies have shown the correlation of high ERCC1 expression and poor response to therapy across different tumor types. In most of these studies, the antibody used to assess ERCC1 expression has been the monoclonal 8F1 antibody.

See also

- ERCCs
- excision repair

References

- Detection of ERCC1 118 polymorphisms in non-small-cell lung cancer by an improved fluorescence polarization assay. Wenchao L, Xiaohui L, Yan X, Helong Z, Wenzhao Y, Yanhai G, Zhen Y, Ju Z. Diagn Mol Pathol. 2010 Sep;19(3):164-8. PMID: 20736746

- Jaspers NG, Raams A, Silengo MC, Wijgers N, Niedernhofer LJ, Robinson AR, Giglia-Mari G, Hoogstraten D, Kleijer WJ, Hoeijmakers JH, Vermeulen W. First reported patient with human ERCC1 deficiency has cerebro-oculo-facio-skeletal syndrome with a mild defect in nucleotide excision repair and severe developmental failure. Am J Hum Genet. 2007 Mar;80(3):457-66. PMID: 17273966