BRCA1 Alternative splicing landscape in breast tissue samples

BMC Cancer

Miguel de la Hoya¹  Trinidad Caldés¹  Eduardo Díaz-Rubio⁴  Joaquín Dopazo²  Esperanza Benito³  Patricia Ayllón¹  Pilar Garre¹  José A García-Sáenz⁴  Gorka Ruiz de Garibay¹  Irene López-Perolio¹  Francisco García-García¹  Atocha Romero¹ 

[1]Breast Cancer and Systems Biology Unit, Translational Research Laboratory, Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L’Hospitalet del Llobregat, Instituto Carlos III, Spanish Ministry of Economy and Competitivy, Barcelona 08908, Spain

[2]Centre for Biomedical Network Research on Rare Diseases (CIBERER), Valencia, Spain

[3]Plastic Surgery Department, Hospital Clínico San Carlos, Madrid, Spain

[4]Medical Oncology Department. Hospital Clínico San Carlos. Department of Medicine. Faculty of Medicine, Universidad Complutense Madrid, Madrid, Spain

关键词: Breast cancer;    Splicing;    BRCA1;   

Others  :  1161222
DOI  :  10.1186/s12885-015-1145-9

 received in 2014-10-09, accepted in 2015-02-27,  发布年份 2015

【 摘 要 】

Background

BRCA1 is a key protein in cell network, involved in DNA repair pathways and cell cycle. Recently, the ENIGMA consortium has reported a high number of alternative splicing (AS) events at this locus in blood-derived samples. However, BRCA1 splicing pattern in breast tissue samples is unknown. Here, we provide an accurate description of BRCA1 splicing events distribution in breast tissue samples.

Methods

BRCA1 splicing events were scanned in 70 breast tumor samples, 4 breast samples from healthy individuals and in 72 blood-derived samples by capillary electrophoresis (capillary EP). Molecular subtype was identified in all tumor samples. Splicing events were considered predominant if their relative expression level was at least the 10% of the full-length reference signal.

Results

54 BRCA1 AS events were identified, 27 of them were annotated as predominant in at least one sample. Δ5q, Δ13, Δ9, Δ5 and ▼1aA were significantly more frequently annotated as predominant in breast tumor samples than in blood-derived samples. Predominant splicing events were, on average, more frequent in tumor samples than in normal breast tissue samples (P = 0.010). Similarly, likely inactivating splicing events (PTC-NMDs, Non-Coding, Δ5 and Δ18) were more frequently annotated as predominant in tumor than in normal breast samples (P = 0.020), whereas there were no significant differences for other splicing events (No-Fs) frequency distribution between tumor and normal breast samples (P = 0.689).

Conclusions

Our results complement recent findings by the ENIGMA consortium, demonstrating that BRCA1 AS, despite its tremendous complexity, is similar in breast and blood samples, with no evidences for tissue specific AS events. Further on, we conclude that somatic inactivation of BRCA1 through spliciogenic mutations is, at best, a rare mechanism in breast carcinogenesis, albeit our data detects an excess of likely inactivating AS events in breast tumor samples.

【 授权许可】

   
2015 Romero et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

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