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Chemotherapy induce...
Chemotherapy induced microsatellite instability and loss of heterozygosity in chromosomes 2, 5, 10, and 17 in solid tumor patients
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- Kamat, Nasir, 1970- (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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- Khidhir, Mohammed (författare)
- Management of Natural Conservation , UAE
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- Hussain, Sabir (författare)
- Oncology department, Tawam Hospital, UAE
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visa fler...
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- Alashari, Mouied (författare)
- Pathology Department, Tawam hospital, UAE
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- Rannug, Ulf (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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visa färre...
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(creator_code:org_t)
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- Objectives: The aim of the studywas to evaluate chemotherapy-related microsatellite instability (MSI), loss of heterozygosity (LOH), and loss of mismatch repair (MMR) expression in solid tumor patients. Methods: Samples were collected from 117 de novo patients with solid tumors of different origins. Specimens, taken pre- and post-treatment, were screened for MSI and LOH in 10 microsatellite sequences in blood, and expression of five MMR proteins were analyzed in cancer tissues using immunohistochemistry. Results: Microsatellite analysis showed that 66.7% of the patients had MSI, including 23.1% high-positive MSI and 43.6% low-positive MSI. A large portion (41%) of the patients exhibited LOH in addition to MSI. MSI and LOH were detected in seven loci in which incidence rates ranged from 3.8% positive for Bat-26 to 34.6% positive for Tp53-Alu. Immunohistochemistry revealed that human mutL homolog 1 (hMLH1) expression was deficient in 29.1% of the patients, whereas18.8%, 23.9%, 13.4%, and 9.7% were deficient for human mutS homolog 2(hMSH2), P53, human mutS homolog 6 (hMSH6) and human post-meiotic segregation increased 2 (hPMS2), respectively. There was a significant correlation between MSI and LOH incidence in Tp53-Alu, Mfd41, and APC with low or deficient expression of hMLH1, hMSH2, and P53. A significant association between MSI and LOH, and incidence of secondary tumors was also evident. Conclusions: The negative correlation between MMR expression, MSI, and LOH and increased resistance to anti-cancer drugs and development of secondary cancers demonstrates a useful aid in early detection of potential chemotherapy-related side-effects. The diagnostic value demonstrated in our earlier study on breast cancer patients was confirmed for other solid tumors.
Ämnesord
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
Nyckelord
- Chemotherapy
- genetic instability
- microsatellites
- mismatch repair
- secondary tumors
- molekylärgenetik
- Molecular Genetics
Publikations- och innehållstyp
- vet (ämneskategori)
- ovr (ämneskategori)