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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2017

Open Access 01-05-2017 | Epidemiology

Characteristics of BRCA1/2 mutations carriers including large genomic rearrangements in high risk breast cancer patients

Authors: Boyoung Park, Ji Yeon Sohn, Kyong-Ah Yoon, Keun Seok Lee, Eun Hae Cho, Myong Cheol Lim, Moon Jung Yang, Soo Jin Park, Moo Hyun Lee, See youn Lee, Yoon Jung Chang, Dong Ock Lee, Sun-Young Kong, Eun Sook Lee

Published in: Breast Cancer Research and Treatment | Issue 1/2017

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Abstract

Purpose

We investigated the prevalence of BRCA1/2 small mutations and large genomic rearrangements in high risk breast cancer patients who attended a genetic counseling clinic.

Methods

In total 478 patients were assessed for BRCA1/2 mutations by direct sequencing, of whom, 306 were identified as non-carriers of BRCA1/2 mutation and assessed for large rearrangement mutations by multiplex ligation-dependent probe amplification. Family history and clinicopathological characteristics of patients were evaluated.

Results

Sixty-three mutation carriers (13.2%) were identified with BRCA1 mutations (6.3%) and BRCA2 mutations (6.9%), respectively. Mutation frequency was affected by familial and personal factors. Breast cancer patients with family history of breast and ovarian cancer showed the highest prevalence of BRCA1/2 mutations (67%), and triple-negative breast cancer (TNBC) patients showed high BRCA1 mutation prevalence (25%). The three probands of BRCA1 deletion (1%) represented both familial risk and personal or clinicopathological risk factors as two with TNBC and one with bilateral ovarian cancer.

Discussion

This is the largest study assessing large genomic rearrangement prevalence in Korea and BRCA1 deletion frequency was low as 1% in patients without BRCA1/2 small mutations. For clinical utility of large genomic rearrangement testing needs further study.
Appendix
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Literature
1.
Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet 62(3):676–689CrossRefPubMedPubMedCentral
2.
Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A et al (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72(5):1117–1130CrossRefPubMedPubMedCentral
3.
4.
Foulkes WD, Smith IE, Reis-Filho JS (2010) Triple-negative breast cancer. N Engl J Med 363(20):1938–1948CrossRefPubMed
5.
NCCN: Genetic/Familial High-Risk Assessment: Breast and Ovarian. 2015, Version 1
6.
Moyer VA (2014) Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 160(4):271–281CrossRefPubMed
7.
Judkins T, Rosenthal E, Arnell C, Burbidge LA, Geary W, Barrus T, Schoenberger J, Trost J, Wenstrup RJ, Roa BB (2012) Clinical significance of large rearrangements in BRCA1 and BRCA2. Cancer 118(21):5210–5216CrossRefPubMedPubMedCentral
8.
Sluiter MD, van Rensburg EJ (2011) Large genomic rearrangements of the BRCA1 and BRCA2 genes: review of the literature and report of a novel BRCA1 mutation. Breast Cancer Res Treat 125(2):325–349CrossRefPubMed
9.
Seong MW, Cho SI, Kim KH, Chung IY, Kang E, Lee JW, Park SK, Lee MH, Choi DH, Yom CK et al (2014) A multi-institutional study of the prevalence of BRCA1 and BRCA2 large genomic rearrangements in familial breast cancer patients. BMC Cancer 14:645CrossRefPubMedPubMedCentral
10.
Seong MW, Cho SI, Noh DY, Han W, Kim SW, Park CM, Park HW, Kim SY, Kim JY, Park SS (2009) Low contribution of BRCA1/2 genomic rearrangement to high-risk breast cancer in the Korean population. Fam Cancer 8(4):505–508CrossRefPubMed
11.
Ewald IP, Ribeiro PL, Palmero EI, Cossio SL, Giugliani R, Ashton-Prolla P (2009) Genomic rearrangements in BRCA1 and BRCA2: a literature review. Genet Mol Biol 32(3):437–446CrossRefPubMedPubMedCentral
12.
Kang P, Mariapun S, Phuah SY, Lim LS, Liu J, Yoon SY, Thong MK, Mohd Taib NA, Yip CH, Teo SH (2010) Large BRCA1 and BRCA2 genomic rearrangements in Malaysian high risk breast-ovarian cancer families. Breast Cancer Res Treat 124(2):579–584CrossRefPubMed
13.
Montagna M, Dalla Palma M, Menin C, Agata S, De Nicolo A, Chieco-Bianchi L, D’Andrea E (2003) Genomic rearrangements account for more than one-third of the BRCA1 mutations in northern Italian breast/ovarian cancer families. Hum Mol Genet 12(9):1055–1061CrossRefPubMed
14.
Palma MD, Domchek SM, Stopfer J, Erlichman J, Siegfried JD, Tigges-Cardwell J, Mason BA, Rebbeck TR, Nathanson KL (2008) The relative contribution of point mutations and genomic rearrangements in BRCA1 and BRCA2 in high-risk breast cancer families. Cancer Res 68(17):7006–7014CrossRefPubMedPubMedCentral
15.
Chen S, Wang W, Broman KW, Katki HA, Parmigiani G (2004) BayesMendel: an R environment for Mendelian risk prediction. Stat Appl Genet Mol Biol 3(1):1063
16.
Parmigiani G, Berry DA, Aguilar O (1998) Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2. Am J Hum Genet 62(1):145–158CrossRefPubMedPubMedCentral
17.
Frank TS, Deffenbaugh AM, Reid JE, Hulick M, Ward BE, Lingenfelter B, Gumpper KL, Scholl T, Tavtigian SV, Pruss DR (2002) Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol 20(6):1480–1490CrossRefPubMed
18.
Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE (2008) Committee MSotALQA: ACMG recommendations for standards for interpretation and reporting of sequence variations: revisions 2007. Genet Med 10(4):294–300CrossRefPubMed
19.
Ahn SH, Son BH, Yoon KS, Noh DY, Han W, Kim SW, Lee ES, Park HL, Hong YJ, Choi JJ et al (2007) BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk of carrying mutations. Cancer Lett 245(1–2):90–95CrossRefPubMed
20.
Han SA, Kim SW, Kang E, Park SK, Ahn SH, Lee MH, Nam SJ, Han W, Bae YT, Kim HA et al (2013) The prevalence of BRCA mutations among familial breast cancer patients in Korea: results of the Korean Hereditary Breast Cancer study. Fam Cancer 12(1):75–81CrossRefPubMed
21.
Kang E, Seong MW, Park SK, Lee JW, Lee J, Kim LS, Lee JE, Kim SY, Jeong J, Han SA et al (2015) The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean Hereditary Breast Cancer (KOHBRA) study. Breast Cancer Res Treat 151(1):157–168CrossRefPubMed
22.
Seong MW, Cho S, Noh DY, Han W, Kim SW, Park CM, Park HW, Kim SY, Kim JY, Park SS (2009) Comprehensive mutational analysis of BRCA1/BRCA2 for Korean breast cancer patients: evidence of a founder mutation. Clin Genet 76(2):152–160CrossRefPubMed
23.
24.
Son BH, Ahn SH, Kim SW, Kang E, Park SK, Lee MH, Noh WC, Kim LS, Jung Y, Kim KS et al (2012) Prevalence of BRCA1 and BRCA2 mutations in non-familial breast cancer patients with high risks in Korea: the Korean Hereditary Breast Cancer (KOHBRA) Study. Breast Cancer Res Treat 133(3):1143–1152CrossRefPubMedPubMedCentral
25.
Choi DH, Lee MH, Bale AE, Carter D, Haffty BG (2004) Incidence of BRCA1 and BRCA2 mutations in young Korean breast cancer patients. J Clin Oncol 22(9):1638–1645CrossRefPubMed
26.
El Saghir NS, Zgheib NK, Assi HA, Khoury KE, Bidet Y, Jaber SM, Charara RN, Farhat RA, Kreidieh FY, Decousus S (2015) BRCA1 and BRCA2 mutations in ethnic Lebanese Arab women with high hereditary risk breast cancer. Oncologist 20(4):357–364CrossRefPubMedPubMedCentral
27.
Konecny M, Milly M, Zavodna K, Weismanova E, Gregorova J, Mlkva I, Ilencikova D, Kausitz J, Bartosova Z (2011) Comprehensive genetic characterization of hereditary breast/ovarian cancer families from Slovakia. Breast Cancer Res Treat 126(1):119–130CrossRefPubMed
28.
Kwong A, Chen J, Shin VY, Ho JC, Law FB, Au CH, Chan T-L, Ma ES, Ford JM (2015) The importance of analysis of long-range rearrangement of BRCA1 and BRCA2 in genetic diagnosis of familial breast cancer. Cancer Genet 208(9):448–454CrossRefPubMed
29.
Lim Y, Iau P, Ali A, Lee S, Wong JL, Putti T, Sng JH (2007) Identification of novel BRCA large genomic rearrangements in Singapore Asian breast and ovarian patients with cancer. Clin Genet 71(4):331–342CrossRefPubMed
30.
Ratajska M, Brozek I, Senkus-Konefka E, Jassem J, Stepnowska M, Palomba G, Pisano M, Casula M, Palmieri G, Borg A (2008) BRCA1 and BRCA2 point mutations and large rearrangements in breast and ovarian cancer families in Northern Poland. Oncol Rep 19(1):263PubMed
31.
Rudnicka H, Debniak T, Cybulski C, Huzarski T, Gronwald J, Lubinski J, Gorski B (2013) Large BRCA1 and BRCA2 genomic rearrangements in Polish high-risk breast and ovarian cancer families. Mol Biol Rep 40(12):6619–6623CrossRefPubMed
32.
Sharifah NA, Nurismah MI, Lee HC, Aisyah AN, Clarence-Ko CH, Naqiyah I, Rohaizak M, Fuad I, Jamal ARA, Zarina AL (2010) Identification of novel large genomic rearrangements at the BRCA1 locus in Malaysian women with breast cancer. Cancer Epidemiol 34(4):442–447CrossRefPubMed
33.
Villarreal-Garza C, Alvarez-Gómez RM, Pérez-Plasencia C, Herrera LA, Herzog J, Castillo D, Mohar A, Castro C, Gallardo LN, Gallardo D (2015) Significant clinical impact of recurrent BRCA1 and BRCA2 mutations in Mexico. Cancer 121(3):372–378CrossRefPubMed
Metadata
Title
Characteristics of BRCA1/2 mutations carriers including large genomic rearrangements in high risk breast cancer patients
Authors
Boyoung Park
Ji Yeon Sohn
Kyong-Ah Yoon
Keun Seok Lee
Eun Hae Cho
Myong Cheol Lim
Moon Jung Yang
Soo Jin Park
Moo Hyun Lee
See youn Lee
Yoon Jung Chang
Dong Ock Lee
Sun-Young Kong
Eun Sook Lee
Publication date
01-05-2017
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4142-7

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