BACKGROUND: Although most BRCA sequence variants are clearly deleterious and unequivocally pathogenetic, several are still classified as variants of unknown significance. PATIENTS AND METHODS: We followed families undergoing oncogenetic counseling from risk identification to risk definition by genetic testing and risk management. RESULTS: We identified two germline mutations in the BRCA2 gene in a woman with breast and ovarian cancer. One sequence alteration was 859/G>A in exon 7 (V211I). The other second sequence alteration (IVS13-2A>T) affected the splicing site in intron 13. The latter alteration is not yet listed in the Breast Cancer Information Core database. RT-PCR resulted in transcription of a sequence lacking exon 7 and a subsequent anomalous stop codon in exon 9 thereby confirming altered messenger RNA (mRNA) maturation. Amplification of the mutation in intron 13 resulted in transcription of a sequence lacking exon 14 and an anomalous stop codon in exon 15 thereby confirming altered mRNA maturation. Both mutations led to a truncated BRCA2 protein in its carboxy-terminal region. CONCLUSION: The two BRCA2 mutations identified affect mRNA splicing fidelity and play a pathogenetic role in breast and ovarian cancer

Two mutations of BRCA2 gene at exon and splicing site in a woman who underwent oncogenetic counseling

PEPE, Stefano;
2009-01-01

Abstract

BACKGROUND: Although most BRCA sequence variants are clearly deleterious and unequivocally pathogenetic, several are still classified as variants of unknown significance. PATIENTS AND METHODS: We followed families undergoing oncogenetic counseling from risk identification to risk definition by genetic testing and risk management. RESULTS: We identified two germline mutations in the BRCA2 gene in a woman with breast and ovarian cancer. One sequence alteration was 859/G>A in exon 7 (V211I). The other second sequence alteration (IVS13-2A>T) affected the splicing site in intron 13. The latter alteration is not yet listed in the Breast Cancer Information Core database. RT-PCR resulted in transcription of a sequence lacking exon 7 and a subsequent anomalous stop codon in exon 9 thereby confirming altered messenger RNA (mRNA) maturation. Amplification of the mutation in intron 13 resulted in transcription of a sequence lacking exon 14 and an anomalous stop codon in exon 15 thereby confirming altered mRNA maturation. Both mutations led to a truncated BRCA2 protein in its carboxy-terminal region. CONCLUSION: The two BRCA2 mutations identified affect mRNA splicing fidelity and play a pathogenetic role in breast and ovarian cancer
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11386/3104433
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact