Breast Cancer

, Volume 24, Issue 2, pp 336–340

OLA1 gene sequencing in patients with BRCA1/2 mutation-negative suspected hereditary breast and ovarian cancer

  • Masanobu Takahashi
  • Natsuko Chiba
  • Hideki Shimodaira
  • Yuki Yoshino
  • Takahiro Mori
  • Makiko Sumii
  • Tadashi Nomizu
  • Chikashi Ishioka
Original Article

Abstract

Background

Of individuals with suspected hereditary breast and ovarian cancer (HBOC), approximately 30–70 % do not harbor mutations in either BRCA1 or BRCA2 gene, which suggests that these individuals have other genetic or epigenetic alterations that could lead to the onset of this hereditary disease. We have recently identified OLA1 as a novel BRCA1/BARD1-interacting protein. In the present study, we aimed to elucidate whether any genetic mutations in OLA1 are detected among patients with suspected HBOC without BRCA1 or BRCA2 mutations.

Methods

Among 53 patients with suspected HBOC enrolled at Hoshi General Hospital, 23 patients without any BRCA1 or BRCA2 mutations were analyzed for OLA1 mutations. Genomic DNA was extracted from the peripheral blood samples. PCR and Sanger sequencing were performed to elucidate whether there were any mutations in any of the ten exons and flanking introns of the OLA1 gene.

Results

No germline sequence variation was detected in the OLA1 gene among the 23 patients enrolled in this study.

Conclusions

No germline mutations were found in the OLA1 gene among the cohort of patients with suspected HBOC without BRCA1 or BRCA2 mutations. Further studies are needed to clarify whether other mutations/epigenetic alterations are involved in the pathogenesis of BRCA1 or BRCA2 mutation-negative inherited disease with breast or ovarian cancer.

Keywords

OLA1 Hereditary breast and ovarian cancer BRCA1 BRCA2 

References

  1. 1.
    Cancer Statistics in Japan 2014. Foundation for Promotion of Cancer Research (FPCR): Tokyo, Japan; 2015. p. 115.Google Scholar
  2. 2.
    Nakamura S, Takahashi M, Tozaki M, Nakayama T, Nomizu T, Miki Y, et al. Prevalence and differentiation of hereditary breast and ovarian cancers in Japan. Breast Cancer. 2015;22:462–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Shiovitz S, Korde LA. Genetics of breast cancer: a topic in evolution. Ann Oncol. 2015;26:1291–9.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Michailidou K, Beesley J, Lindstrom S, Canisius S, Dennis J, Lush MJ, et al. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer. Nat Genet. 2015;47:373–80.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Michailidou K, Hall P, Gonzalez-Neira A, Ghoussaini M, Dennis J, Milne RL, et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet. 2013;45:353–61 (61e1–2).CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Ransburgh DJ, Chiba N, Ishioka C, Toland AE, Parvin JD. Identification of breast tumor mutations in BRCA1 that abolish its function in homologous DNA recombination. Cancer Res. 2010;70:988–95.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Matsuzawa A, Kanno S, Nakayama M, Mochiduki H, Wei L, Shimaoka T, et al. The BRCA1/BARD1-interacting protein OLA1 functions in centrosome regulation. Mol Cell. 2014;53:101–14.CrossRefPubMedGoogle Scholar
  8. 8.
    Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, et al. The consensus coding sequences of human breast and colorectal cancers. Science. 2006;314:268–74.CrossRefPubMedGoogle Scholar
  9. 9.
    Kais Z, Chiba N, Ishioka C, Parvin JD. Functional differences among BRCA1 missense mutations in the control of centrosome duplication. Oncogene. 2012;31:799–804.CrossRefPubMedGoogle Scholar
  10. 10.
    Han X, Saito H, Miki Y, Nakanishi A. A CRM1-mediated nuclear export signal governs cytoplasmic localization of BRCA2 and is essential for centrosomal localization of BRCA2. Oncogene. 2008;27:2969–77.CrossRefPubMedGoogle Scholar
  11. 11.
    Katagiri T, Kasumi F, Yoshimoto M, Nomizu T, Asaishi K, Abe R, et al. High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese breast cancer families. J Hum Genet. 1998;43:42–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Sakayori M, Kawahara M, Shiraishi K, Nomizu T, Shimada A, Kudo T, et al. Evaluation of the diagnostic accuracy of the stop codon (SC) assay for identifying protein-truncating mutations in the BRCA1and BRCA2genes in familial breast cancer. J Hum Genet. 2003;48:130–7.PubMedGoogle Scholar
  13. 13.
    Economopoulou P, Dimitriadis G, Psyrri A. Beyond BRCA: new hereditary breast cancer susceptibility genes. Cancer Treat Rev. 2015;41:1–8.CrossRefPubMedGoogle Scholar
  14. 14.
    De Brakeleer S, De Greve J, Loris R, Janin N, Lissens W, Sermijn E, et al. Cancer predisposing missense and protein truncating BARD1 mutations in non-BRCA1 or BRCA2 breast cancer families. Hum Mutat. 2010;31:E1175–85.CrossRefPubMedGoogle Scholar
  15. 15.
    Ratajska M, Antoszewska E, Piskorz A, Brozek I, Borg A, Kusmierek H, et al. Cancer predisposing BARD1 mutations in breast-ovarian cancer families. Breast Cancer Res Treat. 2012;131:89–97.CrossRefPubMedGoogle Scholar
  16. 16.
    Sun H, Luo X, Montalbano J, Jin W, Shi J, Sheikh MS, et al. DOC45, a novel DNA damage-regulated nucleocytoplasmic ATPase that is overexpressed in multiple human malignancies. Mol Cancer Res. 2010;8:57–66.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Breast Cancer Society 2016

Authors and Affiliations

  • Masanobu Takahashi
    • 1
    • 2
  • Natsuko Chiba
    • 3
  • Hideki Shimodaira
    • 1
    • 2
  • Yuki Yoshino
    • 3
  • Takahiro Mori
    • 2
  • Makiko Sumii
    • 1
  • Tadashi Nomizu
    • 4
  • Chikashi Ishioka
    • 1
    • 2
  1. 1.Department of Clinical Oncology, Institute of Development, Aging and CancerTohoku UniversityMiyagiJapan
  2. 2.Department of Medical OncologyTohoku University HospitalMiyagiJapan
  3. 3.Department of Cancer Biology, Institute of Development, Aging and CancerTohoku UniversityMiyagiJapan
  4. 4.Department of Surgery, Breast Cancer Center, Familial Tumor ClinicHoshi General HospitalHukushimaJapan

Personalised recommendations