Dominant negative ATM mutationsn in breast cancer families

J 2002

Dominant negative ATM mutationsn in breast cancer families

LEI, Haixin, Daria POSPÍŠILOVÁ, Arnica LINDBLOM a Igor VOŘECHOVSKÝ

Základní údaje

Originální název

Dominant negative ATM mutationsn in breast cancer families

Autoři

LEI, Haixin (752 Švédsko), Daria POSPÍŠILOVÁ (203 Česká republika), Arnica LINDBLOM (752 Švédsko) a Igor VOŘECHOVSKÝ (203 Česká republika, garant)

Vydání

Journal of the National Cancer Institute, Bethesda, National Cancer Institute, 2002, 0027-8874

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 14.500

Kód RIV

RIV/00216224:14110/02:00007646

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

breast cancer; ATM

Štítky

ATM, breast cancer

Změněno: 15. 5. 2003 18:07, Mgr. Daria Strouhalová, Ph.D.

Anotace

V originále

Breast cancer is the most frequent malignancy in women in the world, with a cumulative lifetime risk estimated to be 10-12%. Cytogenic and molecular genetic analyses of breast tumor cells suggest that the development of human breast cancer involves the accumulation of alterations in genes which normally serve to control growth and differentiation. One type of this alteration is loss of heterozygosity (LOH), which is detected in many cases of breast cancer. LOH of tumor suppressor genes are associated with cancerogenesis. Several studies have indicated that the genes harbors on long arm of chromosome 11, could be detected during tumorogenesis. Deletions at 11q23 were detected in variety of human neoplasma, including breast. In this region can be harbor at least one tumor suppressor gene, which is inactivated during the establishment or progression of several types of tumors. Evidence for the existence of a tumor suppresor gene(s) in this region came from the observation that tumorgenicity of the MCF-7 cell line is inhibited by the introduction of the segment 11q13-q23 of the normal human chromosome 11. One of the candidate gene is A-T (ataxia-teleangiectasia) gene, located at chromosomal region 11q22-q23. Patients carrying two mutant alleles (ATM) and affected by A-T a 100-fold higher risk of developing cancer, moustly leukemias and lymphomas, than unaffected age-matched subjects. Heterozygous A-T carriers have a 3,1 and 2,3 (females and males) fold increases risk of cancer, in particular breast cancer, compared to the normal population. IT is estimated, that asuch as 8% of sporadic breast cancer could possibly develop in carriers of ATM gene predisposition mutations. It seems that inherited mutations in ATM gene are responsible for a certain proportion of breast cancer cases, and that LOH of other allele will unmask such a recessive mutation. The ATM gene spans - 150kb genomic sequence and contains 66 exons. It is expressed as 12 kb transcript in all tissues and cell types. This gene is implicated in cell cycle regulation, control of telomere length, and response to DNA danage. The enzyme cooperates with many protein in cell. Its inactivation could be influenced repair process in cell. We interested in catalytic domain as candidate region for inactivation of kinase activity. This part of protein corresponds with last 16 exons on DNA of this gene. Tumor DNA from 42 patients with primary breast cancer were studied. This samples were choosen after analyzed for lost of one alele (part of chromosome) in region 11q22-q23 by methods which detected polymorphic makers on pair of chromosomes. For LOH detection we used SSCP (single-strand conformation polymorphism) and silver staining method. We did not found any unique SSCP variants.

Návaznosti

MSM 141100002, záměr

Název: Molekulární patofyziologie multigenních chorob

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Molekulární patofyziologie multigenních chorob

Citovat

LEI, Haixin, Daria POSPÍŠILOVÁ, Arnica LINDBLOM a Igor VOŘECHOVSKÝ. Dominant negative ATM mutationsn in breast cancer families. Journal of the National Cancer Institute. Bethesda: National Cancer Institute, 2002, roč. 94, č. 12, s. 951-952. ISSN 0027-8874.

@article{485289,
   author = {Lei, Haixin and Pospíšilová, Daria and Lindblom, Arnica and Vořechovský, Igor},
   article_location = {Bethesda},
   article_number = {12},
   keywords = {breast cancer; ATM},
   language = {eng},
   issn = {0027-8874},
   journal = {Journal of the National Cancer Institute},
   title = {Dominant negative ATM mutationsn in breast cancer families},
   volume = {94},
   year = {2002}
}

TY  - JOUR
ID  - 485289
AU  - Lei, Haixin - Pospíšilová, Daria - Lindblom, Arnica - Vořechovský, Igor
PY  - 2002
TI  - Dominant negative ATM mutationsn in breast cancer families
JF  - Journal of the National Cancer Institute
VL  - 94
IS  - 12
SP  - 951
EP  - 951
PB  - National Cancer Institute
SN  - 00278874
KW  - breast cancer
KW  - ATM
N2  - Breast cancer is the most frequent malignancy in women in the world, with a cumulative lifetime risk estimated to be 10-12%. Cytogenic and molecular genetic analyses of breast tumor cells suggest that the development of human breast cancer involves the accumulation of alterations in genes which normally serve to control growth and differentiation. One type of this alteration is loss of heterozygosity (LOH), which is detected in many cases of breast cancer. LOH of tumor suppressor genes are associated with cancerogenesis. Several studies have indicated that the genes harbors on long arm of chromosome 11, could be detected during tumorogenesis. Deletions at 11q23 were detected in variety of human neoplasma, including breast. In this region can be harbor at least one tumor suppressor gene, which is inactivated during the establishment or progression of several types of tumors. Evidence for the existence of a tumor suppresor gene(s) in this region came from the observation that tumorgenicity of the MCF-7 cell line is inhibited by the introduction of the segment 11q13-q23 of the normal human chromosome 11. One of the candidate gene is A-T (ataxia-teleangiectasia) gene, located at chromosomal region 11q22-q23. Patients carrying two mutant alleles (ATM) and affected by A-T a 100-fold higher risk of developing cancer, moustly leukemias and lymphomas, than unaffected age-matched subjects. Heterozygous A-T carriers have a 3,1 and 2,3 (females and males) fold increases risk of cancer, in particular breast cancer, compared to the normal population. IT is estimated, that asuch as 8% of sporadic breast cancer could possibly develop in carriers of ATM gene predisposition mutations. It seems that inherited mutations in ATM gene are responsible for a certain proportion of breast cancer cases, and that LOH of other allele will unmask such a recessive mutation. The ATM gene spans - 150kb genomic sequence and contains 66 exons. It is expressed as 12 kb transcript in all tissues and cell types. This gene is implicated in cell cycle regulation, control of telomere length, and response to DNA danage. The enzyme cooperates with many protein in cell. Its inactivation could be influenced repair process in cell. We interested in catalytic domain as candidate region for inactivation of kinase activity. This part of protein corresponds with last 16 exons on DNA of this gene. Tumor DNA from 42 patients with primary breast cancer were studied. This samples were choosen after analyzed for lost of one alele (part of chromosome) in region 11q22-q23 by methods which detected polymorphic makers on pair of chromosomes. For LOH detection we used SSCP (single-strand conformation polymorphism) and silver staining method. We did not found any unique SSCP variants.
ER  -

LEI, Haixin, Daria POSPÍŠILOVÁ, Arnica LINDBLOM a Igor VOŘECHOVSKÝ. Dominant negative ATM mutationsn in breast cancer families. \textit{Journal of the National Cancer Institute}. Bethesda: National Cancer Institute, 2002, roč.~94, č.~12, s.~951-952. ISSN~0027-8874.

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