Kromosomske aberacije i rak

undergraduate thesis

• Title (english): Chromosomal aberrations and cancer
• Author: Stanka Sudar
• Mentor: Mirjana Pavlica (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2009, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Strukturne promjene ili kromosomske aberacije uključuju delecije, duplikacije, inverzije, izokromosom i translokacije. Delecija je posljedica loma i gubitka kromosomskog segmenta. Duplikacija kromosomskog segmenta nastaje nepravilnim krosingoverom ili pomakom kromosomskog segmenta na novo mjesto, te sparivanjem i krosingoverom. Inverzije uključuju dva loma, rotaciju za 180º te ponovno spajanje. Izokromosom uzrokuje nastanak metacentričnog kromosoma, te izokromosom za dugi krak pokazuje gubitak kratkog kraka, a kratki krak pokazuje gubitak dugog kraka kromosoma. Postoje recipročne i Robertsonove translokacije te translokacije nastaju izmjenom kromosomskih segmenata nehomolognih kromosoma. Kromosomske translokacije se pojavljuju u različitim tumorima. Iako je translokacija t(14:18) nađena u limfomima B-stanica i leukemijama, nešto drugo mora uzrokovati rak jer preko 50% ljudi ima mali broj B-stanica s translokacijama koje se nikada ne razvijaju u rak. Lokusi gena za antitijela su ta mjesta koja su opasna za protoonkogene. Translokacija protoonkogena c-myc bliže pojačivačkoj regiji gena teškog lanca antitijela također uzrokuje nastanak kancerogene B-stanice rezultirajući Burkittovim limfomom. Translokacija lokusa Bcl-2 je jedna od mnogih mutacija koje također mogu uzrokovati kroničnu mijeloičnu leukemiju. Genski produkt tumor supresor gena p53 i genski produkti bcr/abl, bcl-2 i c-myc utječu na osjetljivost stanica na apoptozu (Canman i Kastan, 1995). Osim što p53 protein igra ulogu u posredovanju prekida staničnog ciklusa u G1 fazi za popravak DNA, p53 također vrši funkcije koje su bitne za uklanjanje oštećenih stanica potičući apoptozu u određenim fiziološkim situacijama. Stanice koje eksprimiraju deregulirani c-myc su osjetljivije na apoptozu. Bijeg od apoptoze je često obilježje stanica raka i asociran je s otpornošću na kemoterapiju (Johnstone i sur., 2002). Proteini iz Bcl-2 obitelji su ključni regulatori unutarnjeg puta apoptoze, kontrolirajući početak za sudjelovanje mašinerije na odgovor na kemijsko oštećenje. Bcl-2 proteini su poželjne mete za stvaranje novih antitumorskih lijekova.

Abstract (english)

Structural changes or chromosomal aberrations include deletions, duplications, inversions, isochromosome and translocations. Deletion is a consequence of a break and lost of chromosomal segment. Duplication of chromosomal segment occurs after irregular crossing-over or shift of chromosomal segment to a new location, and pairing and crossing-over. Inversion include two breaks, rotation of 180º and reconnection. Isochromosome causes the formation of metacentric chromosome and isochromosome the long arm of the loss shows a short-tail, a short arm shows a loss of long arms of chromosomes. There are reciprocal and Robertsonian translocation and translocation of chromosome segments are formed by changing nehomologous chromosomes. Although the t(14:18) translocation is found in B-cell lymphomas and leukemias, something else must contribute to creating the cancer because over 50% of us have small numbers of B-cells with translocation that never progress to cancer. The antibody gene loci are dangerous places for proto-oncogenes to take up residence. Translocation of the proto-oncogene c-myc close to the enhancer of the antibody heavy chain genes also produces cancerous B cells resulting in Burkitt´s lymphoma. The translocation of the Bcl-2 locus is just one of many mutations that can give rise to a chronic lymphocytic leukemia. The p53 tumor suppressor gene product, and the bcr/abl, bcl-2 and c-myc gene products all appear to influence the susceptibility of cells to apoptosis (Canman and Kastan, 1995). In addition to the role p53 protein plays in mediating a cell cycle arrest in G1 following DNA damage, p53 also performs functions critical for removal of damaged cells by initiating apoptosis in certian physiological situations. Cells which express deregulated c-myc are sensitized to apoptosis. An escape from apoptosis is often a hallmark of cancer cells, and is associated to chemotherapy resistance (Johnstone et al., 2002). Proteins from the Bcl-2 family are the key regulators of the intrinsic pathway of apoptosis, controlling the point-of no-return and setting the threshold to engage the death machinery in response to a chemical damage. Therefore, Bcl-2 proteins have emerged as an attractive target to develop novel anticancer drugs.

• Keywords: kromosomske aberacije; rak
• Keywords (english): chromosomal aberrations; cancer
• Language: croatian
• URN:NBN: urn:nbn:hr:217:387345
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-03-16 13:28:12