Novel germline mutations in BRCA2 gene among breast and breast-ovarian cancer families from Poland.
Identification of mutations in the BRCA2 gene and estimation of their clinical consequences for women and men treated in the Maria Sklodowska-Curie Memorial Cancer Center Warsaw, Poland in the years 1998-2008. The probands (97 women and 8 men) had a family history of breast and ovarian cancer (median age 46). The presence of molecular changes was examined in DNA isolated from peripheral blood lymphocytes. Germline mutations in 27 exons of the BRCA2 gene were screened by 'touchdown' PCR amplification, DHPLC and sequencing. Missense mutations were classified by multiple-sequences alignments of orthologous BRCA2 protein sequences with T-Coffee software. 39 molecular changes (8 novel) were identified in the BRCA2 gene in 105 investigated patients. In 12 patients the following pathogenic mutations were identified: 5467insT, 6174delT, 6192delAT, 6675delTA, 8141del5, 9152delT, 9326insA, 9631delC, IVS23-2A > G and E394X. The presence of 10 missense type mutations was detected including the following: D1420O, T1915 M, N3124I. The determination of pathogenic status of molecular variants detected in BRCA2 gene, described in the BIC mutation database as 'UV' depends on many parameters. Important is the assessment of the evolutionary conservation of their protein sequences and studying of the frequency of molecular variants detected in breast cancer patients and in population. A high diversity was found of the pathogenic mutations detected in BRCA2 gene in the Polish population.
Balabas
Aneta
A
Endocrinology Department, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, WK Roentgen 5, 02-781, Warsaw, Poland. abalabas@coi.waw.pl
Skasko
Elzbieta
E
Nowakowska
Dorota
D
Niwinska
Anna
A
Blecharz
Pawel
P
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D005190:Family; D005260:Female; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D011044:Poland; D016133:Polymerase Chain Reaction
Mol Cell. 2001 Feb;7(2):273-82
11239456
Fam Cancer. 2009;8(2):127-33
18798010
Br J Cancer. 2002 Oct 7;87(8):888-91
12373604
J Mol Biol. 2000 Sep 8;302(1):205-17
10964570
Am J Hum Genet. 2007 Nov;81(5):873-83
17924331
Eur J Med Genet. 2008 Mar-Apr;51(2):141-7
18158280
Am J Hum Genet. 2001 Feb;68(2):410-9
11170890
Acta Oncol. 2008;47(4):772-7
18465347
Hum Mutat. 2000 Dec;16(6):482-90
11102977
Oncol Rep. 2005 Jul;14(1):85-8
15944772
Am J Hum Genet. 2004 Oct;75(4):535-44
15290653
Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5287-92
9560268
Hum Mol Genet. 1997 Jan;6(1):53-8
9002670
BMC Cancer. 2007 Sep 03;7:170
17767707
Cancer Res. 1999 Mar 1;59(5):995-8
10070953
Cancer Res. 1998 Apr 1;58(7):1367-71
9537231
BMC Med Genet. 2008 Jul 02;9:58
18597679
Nat Genet. 2000 Nov;26(3):362-4
11062481
Cancer Epidemiol Biomarkers Prev. 2007 Feb;16(2):342-6
17301269
Genomics. 1999 Dec 15;62(3):369-76
10644434
Cancer Res. 2005 Jan 15;65(2):417-26
15695382
Breast Cancer Res. 2005;7(6):R1023-7
16280055
Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):413-6
11927503
Am J Hum Genet. 2003 May;72(5):1117-30
12677558
Hum Mutat. 2001;17(1):73
11139248