02810nas a2200277   4500008004100000022001400041245006700055210006600122260000900188300000800197490000700205520198700212100001902199700002902218700002602247700002802273700002902301700001702330700002202347700002202369700002102391700002502412700002202437700002302459856005002482       2015                        eng d  a1471-240700aBRCA1 Alternative splicing landscape in breast tissue samples.0 aBRCA1 Alternative splicing landscape in breast tissue samples  c2015  a2190 v153 aBACKGROUND: 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.1 aRomero, Atocha1 aGarcia-Garcia, Francisco1 aLópez-Perolio, Irene1 ade Garibay, Gorka, Ruiz1 aGarcía-Sáenz, José, A1 aGarre, Pilar1 aAyllón, Patricia1 aBenito, Esperanza1 aDopazo, Joaquín1 aDíaz-Rubio, Eduardo1 aCaldés, Trinidad1 ade la Hoya, Miguel  uhttp://www.biomedcentral.com/1471-2407/15/219