The spectra of large second-step mutations are similar for two different mouse autosomes.
Loss of tumor suppressor gene expression via mutations plays a critical role in cancer development, particularly when occurring in heterozygous cells. These so-called "second-step" mutational events are often large in size and arise most often from chromosome loss, mitotic recombination, or interstitial deletion. An open question in cancer research is whether different chromosomes are equally susceptible to formation of large mutations, or alternatively if the unique sequence of each chromosome will lead to chromosome-specific mutational spectra. To address this question, the spectra of second-step mutations were determined for chromosomes 8 and 11 in Aprt and Tk mutants, respectively, isolated from primary kidney clones heterozygous for both loci. The results showed that the spectra of large mutational events were essentially the same. This observation suggests that internal and external cellular environments provide the driving force for large autosomal mutational events, and that chromosome structure per se is the substrate upon which these forces act.
Kasameyer
Elizabeth
E
Center for Research on Occupational and Environmental Toxicology (CROET), Oregon Health & Sciences University, Portland, OR 97239, USA.
Connolly
Lanelle
L
Lasarev
Michael
M
Turker
Mitchell S
MS
D000228:Adenine Phosphoribosyltransferase / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002875:Chromosomes; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D011995:Recombination, Genetic; D017384:Sequence Deletion; D013937:Thymidine Kinase / Q000235:genetics
D000228:Adenine Phosphoribosyltransferase; D013937:Thymidine Kinase
Cancer Res. 2002 Mar 1;62(5):1518-23
11888929
Carcinogenesis. 2001 Jul;22(7):1099-106
11408355
Mutat Res. 2002 May 22;502(1-2):69-80
11996974
Mutagenesis. 2003 Jan;18(1):1-6
12473728
Carcinogenesis. 2003 Jan;24(1):139-44
12538359
Chromosome Res. 2004;12(1):15-23
14984098
J Biol Chem. 1969 Sep 10;244(17):4779-84
4309151
Mutat Res. 1978 Jan;49(1):83-94
622085
Cell. 1980 Nov;22(2 Pt 2):479-88
6256082
J Cell Physiol. 1983 Oct;117(1):62-8
6311850
Mol Cell Biol. 1984 Feb;4(2):383-5
6366521
Trends Genet. 1990 Dec;6(12):377-9
2087778
Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3256-60
1565617
Environ Mol Mutagen. 1996;28(4):471-82
8991080
Mutat Res. 1997 Mar 21;374(2):201-8
9100844
Mutat Res. 1998 May 25;400(1-2):135-42
9685614
Nucleic Acids Res. 1998 Nov 1;26(21):4888-94
9776749
Mutat Res. 1999 Jan 25;423(1-2):125-36
10029690
Cancer Res. 1999 Apr 15;59(8):1837-9
10213488
Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9230-5
10430925
Oncogene. 2004 Dec 2;23(56):9017-24
15480418
Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10713-6
16818882
Aging Cell. 2007 Feb;6(1):73-86
17266677
Environ Mol Mutagen. 2007 Apr-May;48(3-4):258-69
16850453
Nature. 2001 Feb 1;409(6820):633-7
11214324
Nat Genet. 2001 Jun;28(2):169-72
11381266
Nat Rev Cancer. 2001 Nov;1(2):157-62
11905807