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Gene Review:

ANKRD30A - ankyrin repeat domain 30A

Homo sapiens

Synonyms: Ankyrin repeat domain-containing protein 30A, NY-BR-1, Serologically defined breast cancer antigen NY-BR-1

Varga, Z. et al., Jäger, D. et al., Jäger, D. et al., Giger, O.T. et al., Jäger, D. et al., et al.

Jäger, Knuth, Varga, Theurillat, Filonenko, Sasse, Odermatt, Jungbluth, Chen, Old, Knuth, Jäger, Moch, Nissan, Jager, Roystacher, Prus, Peretz, Eisenberg, Freund, Scanlan, Ritter, Old, Mitrani-Rosenbaum, Giger, Lacoste, Honegger, Padberg, Moch, Varga, Jäger, Karbach, Pauligk, Seil, Frei, Chen, Old, Knuth, Jäger,

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Disease relevance of ANKRD30A

NY-BR-1 thus represents a breast tissue-specific putative transcription factor with autoimmunogenicity in breast cancer patients [1].
Forty-nine percent of lymph node metastases were NY-BR-1 positive [2].
Sixty percent of invasive breast carcinomas were NY-BR-1 positive, displaying cytoplasmic and/or nuclear immunoreactivity [2].
In tumors, carcinoma in situ and invasive carcinoma of the breast were NY-BR-1 positive whereas other tumors and normal tissues were negative [2].
Strong immunoreactivity for NY-BR-1, a novel breast differentiation antigen, was demonstrated within the epithelial components of the phyllodes tumor [3].

High impact information on ANKRD30A

We have identified a CT antigen, named CTSP-1, with partial similarity to the breast differentiation antigen NY-BR-1 [4].
However, unlike NY-BR-1, NY-BR-1.1 mRNA is expressed in brain, in addition to breast and testis [1].
Using human genome database, NY-BR-1 was localized to chromosome 10p11-p12, and NY-BR-1.1 was tentatively localized to chromosome 9 [1].
Structural analysis of NY-BR-1 cDNA and the corresponding genomic sequences in the recently released working draft of human genome indicated that NY-BR-1 is composed of 37 exons and has an open reading frame of 4.0-4.2 kb, encoding a peptide of Mr 150,000-160,000 [1].
Additional structural features include five tandem ankyrin repeats, implying a role for NY-BR-1 in protein-protein interactions [1].

Anatomical context of ANKRD30A

Furthermore, we were able to identify two HLA-A2 restricted NY-BR-1 epitopes (p158-167 and p960-968) that are recognized by CD8+ T cell clones (NW1100-CTL-7 and NW1100-CTL-43, respectively), as determined by ELISPOT analysis and tetramer staining [5].
RESULTS: Among normal tissues, NY-BR-1 was present solely in ductal epithelium of the breast [2].
Expression of the breast differentiation antigen NY-BR-1 in a phyllodes tumor of the vulva [3].

Other interactions of ANKRD30A

A bipartite nuclear localization signal motif indicates a nuclear site for NY-BR-1, and the presence of a bZIP site (DNA-binding site followed by leucine zipper motif) suggests that NY-BR-1 is a transcription factor [1].
Preferential Nuclear and Cytoplasmic NY-BR-1 Protein Expression in Primary Breast Cancer and Lymph Node Metastases [2].
NY-BR-1 expression was more frequent in estrogen receptor-positive and lymph node-negative primary carcinomas (P < 0.05 each) and was more common in grade 1 (77%) than in grade 2 (63%) or grade 3 (50%) carcinomas (P < 0.05) [2].
We conclude that a multimarker RT-PCR assay probing for NY-BR-1, mammaglobin-B, and CK-19 is more sensitive compared to enhanced pathologic examination [6].

Analytical, diagnostic and therapeutic context of ANKRD30A

The identification of these two naturally processed NY-BR-1-specific CD8+ T cell epitopes opens the perspective for active immunotherapy of HLA-A2 positive patients with NY-BR-1 expressing tumors [5].
However, current data are based on RT-PCR analysis and nothing is known about the presence of NY-BR-1 on a protein level [2].
The organ-specific expression of NY-BR-1 and its high prevalence in metastases indicate that it could be a valuable target for cancer immunotherapy [2].
Another new cancer antigen explored for cancer vaccination is the breast differentiation antigen NY-BR-1, expressed in 70% of all tested primary breast cancers [7].

References

Identification of a tissue-specific putative transcription factor in breast tissue by serological screening of a breast cancer library. Jäger, D., Stockert, E., Güre, A.O., Scanlan, M.J., Karbach, J., Jäger, E., Knuth, A., Old, L.J., Chen, Y.T. Cancer Res. (2001) [Pubmed]
Preferential Nuclear and Cytoplasmic NY-BR-1 Protein Expression in Primary Breast Cancer and Lymph Node Metastases. Varga, Z., Theurillat, J.P., Filonenko, V., Sasse, B., Odermatt, B., Jungbluth, A.A., Chen, Y.T., Old, L.J., Knuth, A., Jäger, D., Moch, H. Clin. Cancer Res. (2006) [Pubmed]
Expression of the breast differentiation antigen NY-BR-1 in a phyllodes tumor of the vulva. Giger, O.T., Lacoste, E., Honegger, C., Padberg, B., Moch, H., Varga, Z. Virchows Arch. (2007) [Pubmed]
Characterization of a cancer/testis (CT) antigen gene family capable of eliciting humoral response in cancer patients. Parmigiani, R.B., Bettoni, F., Vibranovski, M.D., Lopes, M.H., Martins, W.K., Cunha, I.W., Soares, F.A., Simpson, A.J., de Souza, S.J., Camargo, A.A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
Humoral and cellular immune responses against the breast cancer antigen NY-BR-1: definition of two HLA-A2 restricted peptide epitopes. Jäger, D., Karbach, J., Pauligk, C., Seil, I., Frei, C., Chen, Y.T., Old, L.J., Knuth, A., Jäger, E. Cancer Immun. (2005) [Pubmed]
Multimarker RT-PCR assay for the detection of minimal residual disease in sentinel lymph nodes of breast cancer patients. Nissan, A., Jager, D., Roystacher, M., Prus, D., Peretz, T., Eisenberg, I., Freund, H.R., Scanlan, M., Ritter, G., Old, L.J., Mitrani-Rosenbaum, S. Br. J. Cancer (2006) [Pubmed]
Antibodies and vaccines--hope or illusion? Jäger, D., Knuth, A. Breast (Edinburgh, Scotland) (2005) [Pubmed]

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