Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proteins encoded by BRCA1 and ATM may be important in DNA repair and maintenance of genomic integrity. Women heterozygous for a mutation in BRCA1 have an increased incidence of breast cancer. Some evidence also suggests that female carriers of ATM mutations may be susceptible to breast cancer. However, mice carrying one mutant allele of Brca1 or ATM are not highly susceptible to breast cancer. We proposed that heterozygosity for a mutant allele of Brca1 or ATM may confer a decreased ability to repair DNA damage. Such a defect might lead to a heightened sensitivity to tumor development in susceptible animal models. Therefore, mice predispose to mammary tumor development might show an increased susceptibility if they also carry an ATM or Brca1 mutation. C57BL/6J (B6) MIN/+ mice are predisposed to mammary and intestinal tumors and exposure to the point mutagen ethylnitrosourea (ENU) markedly increases mammary tumor multiplicity and incidence. To test our hypothesis, B6.MIN/+ male mice were crossed with 129S6/SvEvTac females heterozygous for a mutant allele of either Brca1 or ATM. Female progeny from each cross were treated with ENU and followed for tumor development. Only MIN/+ F1 females developed mammary tumors and heterozygosity for a mutant Brca1 or ATM allele had no effect on mammary or intestinal tumor incidence and multiplicity. These results suggest that heterozygosity for a mutation in Brca1 or ATM: does not affect MIN-induced tumorigenesis in mice under these conditions. Additionally, exposure to a somatic point mutagen does not increase tumor development in mice carrying Brca1 or ATM mutations.
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PMID:Heterozygosity for a mutation in Brca1 or Atm does not increase susceptibility to ENU-induced mammary tumors in Apc(Min)/+ mice. 1118 58

DNA copy number changes represent molecular fingerprints of solid tumors and are as such relevant for better understanding of tumor development and progression. In this study, we applied genome-wide array comparative genomic hybridization (aCGH) to identify gene-specific DNA copy number changes in chromosomal (CIN)- and microsatellite (MIN)-unstable sporadic colorectal cancers (sCRC). Genomic DNA was extracted from microdissected, matching normal colorectal epithelium and invasive tumor cells of formalin-fixed and paraffin-embedded tissues of 22 cases with colorectal cancer (CIN = 11, MIN = 11). DNA copy number changes were determined by aCGH for 287 target sequences in tumor cell DNAs, using pooled normal DNAs as reference. aCGH data of tumor cell DNAs was confirmed by fluorescence in situ hybridization (FISH) for three genes on serial tissues as those used for aCGH. aCGH revealed DNA copy number changes previously described by metaphase CGH (gains 7, 8q, 13q, and 20q; losses 8p, 15q, 18q, and 17p). However, chromosomal regions 20q, 13q, 7, and 17p were preferentially altered in CIN-type tumors and included DNA amplifications of eight genes on chromosome 20q (TOP1, AIB1, MYBL2, CAS, PTPN1, STK15, ZNF217, and CYP24), two genes on chromosome 13q (BRCA2 and D13S25), and three genes on chromosome 7 (IL6, CYLN2, and MET) as well as DNA deletions of two genes on chromosome 17p (HIC1 and LLGL1). Finally, additional CIN-tumor-associated DNA amplifications were identified for EXT1 (8q24.11) and MYC (8q24.12) as well as DNA deletions for MAP2K5 (15q23) and LAMA3 (18q11.2). In contrast, distinct MIN-tumor-associated DNA amplifications were detected for E2F5 (8p22-q21.3), GARP (11q13.5-q14), ATM (11q22.3), KAL (Xp22.3), and XIST (Xq13.2) as well as DNA deletions for RAF1 (3p25), DCC (18q21.3), and KEN (21q tel). aCGH revealed distinct DNA copy number changes of oncogenes and tumor suppressor genes in CIN- and MIN-type sporadic colorectal carcinomas. The identified candidate genes are likely to have distinct functional roles in the carcinogenesis and progression of CIN- and MIN-type sporadic CRCs and may be involved in the differential response of CIN- and MIN-type tumor cells to (adjuvant) therapy, such as 5-fluorouracil.
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PMID:Array CGH identifies distinct DNA copy number profiles of oncogenes and tumor suppressor genes in chromosomal- and microsatellite-unstable sporadic colorectal carcinomas. 1714 21