[New tumor suppressor genes in hot spots of human chromosome 3: new methods of identification].
Studies of the recent decade, including sequencing of numerous human genome regions, allowed a great progress in detection of new tumor suppressor genes (TSG) and development of new means of their identification and analysis. Effective methods of genome scanning and TSG identification combine DNA array techniques and subtraction hybridization. Alternative ways take advantage of new extrachromosomal vector systems (pETE, pETR) and the functional gene inactivation test. A breakthrough was made in localizing new TSG on the human chromosome 3 short arm, which harbors tumor-suppressing regions and is often rearranged in various tumors and in early carcinogenesis. On 3p, only three putative TSG were known five years ago, and at least ten were identified by the end of 2002. The role of new TSG in carcinogenesis is commonly inferred from a decrease in their transcription in tumor cell lines or primary tumors and from their ability to suppress the growth of these. Protein products of 3p TGS play an important part, constraining cell malignization. Some are directly involved in regulating the cell cycle and inducing apoptosis (RASSFIA), others suppress angiogenesis (Sema3B) or metastasis (Hyal-1). Numerous attempts to find mutations in exons of silent genes failed, and at least half of the new candidate genes (RASSFIA, CACNA2D2, BLU, HYAL1, SEMA3B, RAR-beta) proved to be inactivated by promoter methylation.
State Research Center GosNIIgenetika, Moscow, 113545 Russia. ebraga@genetika.ru
E A
EA
Braga
V I
VI
Kashuba
A V
AV
Maliukova
V I
VI
Loginov
V N
VN
Senchenko
I V
IV
Bazov
L L
LL
Kiselev
E R
ER
Zabarovskiĭ
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D002893:Chromosomes, Human, Pair 3; D019175:DNA Methylation; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D005821:Genetic Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D008175:Lung Neoplasms / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D039961:Semaphorins; D017384:Sequence Deletion; D014161:Transduction, Genetic; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins / Q000235:genetics
D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011498:Protein Precursors; C411762:RASSF1 protein, human; C409766:SEMA3B protein, human; D039961:Semaphorins; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins; C045677:ubiquitin precursor; D015252:Deoxyribonucleases, Type II Site-Specific; C038565:GCGGCCGC-specific type II deoxyribonucleases