Sister chromatid exchange: A possible approach to characterize familial breast cancer patients

De Pascalis,Ivana; Pilato,Brunella; Mazzotta,Annalisa; Dell'Endice,Teresa Stefania; Rubini,Vincenza; Simone,Giovanni; Paradiso,Angelo; Aiello,Vincenzo; Mangia,Anita

doi:10.3892/or.2014.3628

Sister chromatid exchange: A possible approach to characterize familial breast cancer patients

Authors:
- Ivana De Pascalis
- Brunella Pilato
- Annalisa Mazzotta
- Teresa Stefania Dell'Endice
- Vincenza Rubini
- Giovanni Simone
- Angelo Paradiso
- Vincenzo Aiello
- Anita Mangia
View Affiliations

Affiliations: Functional Biomorphology Laboratory, NCRC, IRCSS Istituto Tumori ‘Giovanni Paolo II’, Bari, Italy, Molecular Genetics Laboratory, NCRC, IRCSS Istituto Tumori ‘Giovanni Paolo II’, Bari, Italy, Pathology Department, NCRC, IRCSS Istituto Tumori ‘Giovanni Paolo II’, Bari, Italy, Experimental Medical Oncology, NCRC, IRCSS Istituto Tumori ‘Giovanni Paolo II’, Bari, Italy, Medical Genetics, University of Ferrara, Ferrara, Italy
Published online on: November 26, 2014 https://doi.org/10.3892/or.2014.3628
Pages: 930-934

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Sister chromatid exchange (SCE) frequency is widely used as an indicator of spontaneous chromosome instability. We investigated SCE frequency in the peripheral blood lymphocytes of familial and sporadic breast cancer (BC) patients from the Apulian Caucasian Population. Eighty-one patients were enrolled: 22 with familial history and 59 sporadic patients. Eleven familial patients had an ‘increased risk’ of BRCA gene mutation (BRCAPro ≥10%) and were candidates for BRCA1 and BRCA2 mutation analysis. For these reasons, we stratified the 22 familial BC patients in two group: ‘low-risk’ (n=11) and ‘high-risk’ (n=11) patients for BRCA gene mutations. Two of these 11 ‘high-risk’ patients (18%) had pathogenic mutations in the BRCA2 gene. The subjects were not cigarette smokers or alcohol or drug users, and had no genetic disorders or chronic diseases affecting the family. Our results showed a significant increase in SCE frequency in the familial (5.305±1.088/metaphase) (P<0.0001) and the sporadic patients (3.943±0.552) (P<0.0001) compared to the controls (3.197±0.649). We found that the SCE frequency was always significantly higher in familial than in sporadic patients, regardless of their clinicopathological characteristics. Moreover, we observed that the frequency of SCE in BRCA2 mutation carrier patients was higher compared to patients without mutations in BRCA1/2 genes. These findings highlight an intrinsic genomic instability in familial patients, and we suggest that SCE frequency may be used as a biomarker to better characterize familial BC.

View Figures

View References

1	Pilato B, Martinucci M, Danza K, Pinto R, Petriella D, Lacalamita R, Bruno M, Lambo R, D’Amico C, Paradiso A and Tommasi S: Mutations and polymorphic BRCA variants transmission in breast cancer familial members. Breast Cancer Res Treat. 125:651–657. 2011. View Article : Google Scholar
2	Levin B, Lech D and Friedenson B: Evidence that BRCA1- or BRCA2-associated cancers are not inevitable. Mol Med. 18:1327–1337. 2012. View Article : Google Scholar : PubMed/NCBI
3	O’Donovan PJ and Livingston DM: BRCA1 and BRCA2: breast/ ovarian cancer susceptibility gene products and participants in DNA double-strand break repair. Carcinogenesis. 31:961–967. 2010. View Article : Google Scholar
4	Tekcan A, Elbistan M and Ulusoy AN: Sister chromatid exchanges in breast cancer patients who underwent chemotherapy. J Toxicol Sci. 37:235–243. 2012. View Article : Google Scholar : PubMed/NCBI
5	Conrad S, Künzel J and Löbrich M: Sister chromatid exchanges occur in G2-irradiated cells. Cell Cycle. 10:222–228. 2011. View Article : Google Scholar : PubMed/NCBI
6	White JS, Choi S and Bakkenist CJ: Transient ATM kinase inhibition disrupts DNA damage-induced sister chromatid exchange. Sci Signal. 3:ra442010.PubMed/NCBI
7	Bozsakyova E, Wsolova L and Chalupa I: Spontaneous and gamma-ray-induced sister chromatid exchanges in patients with carcinoma of cervix uteri. Int J Radiat Biol. 81:177–185. 2005. View Article : Google Scholar : PubMed/NCBI
8	Baltaci V, Kayikçioğlu F, Alpas I, Zeyneloğlu H and Haberal A: Sister chromatid exchange rate and alkaline comet assay scores in patients with ovarian cancer. Gynecol Oncol. 84:62–66. 2002. View Article : Google Scholar
9	Dhillon VS and Dhillon IK: Chromosome aberrations and sister chromatid exchange studies in patients with prostate cancer: possible evidence of chromosome instability. Cancer Genet Cytogenet. 100:143–147. 1998. View Article : Google Scholar : PubMed/NCBI
10	Wang LY, Lai MS, Huang SJ, Hsieh CY, Hsu MM and Chen CJ: Increased sister chromatid exchange frequency in peripheral lymphocytes of nasopharyngeal carcinoma and cervical cancer patients. Anticancer Res. 14:105–107. 1994.PubMed/NCBI
11	Dhillon VS, Bhasker R, Kler RS and Husain SA: Sister chromatid exchange (SCE) studies in breast cancer patients: a follow-up study. Cancer Genet Cytogenet. 80:115–117. 1995. View Article : Google Scholar : PubMed/NCBI
12	Roy SK, Trivedi AH, Bakshi SR, Patel RK, Shukla PH, Patel SJ, Bhatavdekar JM, Patel DD and Shah PM: Spontaneous chromosomal instability in breast cancer families. Cancer Genet Cytogenet. 118:52–56. 2000. View Article : Google Scholar : PubMed/NCBI
13	Cefle K, Ucur A, Guney N, Ozturk S, Palanduz S, Tas F, Asoglu O, Bayrak A, Muslumanoglu M and Aydiner A: Increased sister chromatid exchange frequency in young women with breast cancer and in their first-degree relatives. Cancer Genet Cytogenet. 171:65–67. 2006. View Article : Google Scholar : PubMed/NCBI
14	Aristei C, Stracci F, Guerrieri P, Anselmo P, Armellini R, Rulli A, Barberini F, Latini P and Menghini AR: Frequency of sister chromatid exchanges and micronuclei monitored over time in patients with early-stage breast cancer: results of an observational study. Cancer Genet Cytogenet. 192:24–29. 2009. View Article : Google Scholar : PubMed/NCBI
15	Mangia A, Chiriatti A, Tommasi S, Menolascina F, Petroni S, Zito FA, Simone G, Schittulli F and Paradiso A: BRCA1 expression and molecular alterations in familial breast cancer. Histol Histopathol. 24:69–76. 2009.
16	Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM and Hayes DF: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 25:118–145. 2007. View Article : Google Scholar
17	Perry P and Wolff S: New Giemsa method for the differential staining of sister chromatids. Nature. 251:156–158. 1974. View Article : Google Scholar : PubMed/NCBI
18	Hagmar L, Bonassi S, Stromberg U, Brogger A, Knudsen LE, Norppa H and Reuterwall C: Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH). Cancer Res. 58:4117–4121. 1998.PubMed/NCBI
19	Barale R, Chelotti L, Davini T, Del Ry S, Andreassi MG, Ballardin M, Bulleri M, He J, Baldacci S, Di Pede F, Gemignani F and Landi S: Sister chromatid exchange and micronucleus frequency in human lymphocytes of 1,650 subjects in an Italian population: II. Contribution of sex, age, and lifestyle. Environ Mol Mutagen. 31:228–242. 1998. View Article : Google Scholar : PubMed/NCBI
20	Kumar JV, Saraswathi T, Ranganathan K, Umadevi K, Joshua E and Rooban T: Sister chromatid exchanges in smokers and smokers with alcohol habit. J Oral Maxillofac Pathol. 16:338–342. 2012. View Article : Google Scholar : PubMed/NCBI
21	Celik DA, Koşar PA, Ozçelik N and Eroğlu E: Cytogenetic finding of breast cancer cases and in their first-degree relatives. J Breast Cancer. 16:285–290. 2013. View Article : Google Scholar : PubMed/NCBI
22	Ben Salah G, Kamoun H, Rebai A, Ben Youssef A, Ayadi H, Belghith-Mahfoudh N, Fourati A, Ayadi H and Fakhfakh F: Sister chromatid exchange (SCE) and high-frequency cells (HFC) in peripheral blood lymphocytes of healthy Tunisian smokers. Mutat Res. 719:1–6. 2011. View Article : Google Scholar
23	Bernardes de Jesus B and Blasco MA: Telomerase at the intersection of cancer and aging. Trends Genet. 29:513–520. 2013. View Article : Google Scholar : PubMed/NCBI
24	Jacobs PA, Maloney V, Cooke R, Crolla JA, Ashworth A and Swerdlow AJ: Male breast cancer, age and sex chromosome aneuploidy. Br J Cancer. 108:959–963. 2013. View Article : Google Scholar : PubMed/NCBI
25	Trenz K, Lugowski S, Jahrsdörfer U, Jainta S, Vogel W and Speit G: Enhanced sensitivity of peripheral blood lymphocytes from women carrying a BRCA1 mutation towards the mutagenic effects of various cytostatics. Mutat Res. 544:279–288. 2003. View Article : Google Scholar : PubMed/NCBI
26	Kim MK, Zitzmann S, Westermann F, Arnold K, Brouwers S, Schwab M and Savelyeva L: Increased rates of spontaneous sister chromatid exchange in lymphocytes of BRCA2^+/− carriers of familial breast cancer clusters. Cancer Lett. 210:85–94. 2004. View Article : Google Scholar : PubMed/NCBI