Chromosomal imbalances are uncommon in chagasic megaesophagus

Bellini, Marilanda Ferreira; Manzato, Antônio José; Silva, Ana E.; Varella‐Garcia, Marileila

doi:10.1186/1471-230x-10-20

Cited by 6 publications

(6 citation statements)

References 35 publications

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“…Interestingly, a previous study analyzed a series of CM, also from the same region of the present study, for the presence of genomic imbalances in genes relevant in esophageal carcinogenesis, and any significant event was observed. 22 So, TP53 mutations in the conjugation other etiological factors may contribute to cancer development. In fact, our observation of a higher consumption of alcohol and tobacco observed in the ESCC/CM group in comparison with the CM group, supported this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…8,[19][20][21] The studies evaluating the molecular mechanisms underlying this carcinogenic process are scarce. 22 TP53 tumor suppressor gene exhibited a major role in the tumorigenesis of ESCC. 23 TP53 is, by far, the highest mutated gene, with frequencies varying between studies and population, and recently, whole genome sequencing analysis, confirm the high frequency (≈60%) of TP53 mutations.…”

Section: Introductionmentioning

confidence: 99%

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Mutational profile of TP53 in esophageal squamous cell carcinoma associated with chagasic megaesophagus

Lacerda¹,

Cruvinel-Carloni²,

Oliveira³

et al. 2017

Diseases of the Esophagus

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Chaga's disease is an important communicable neglected disease that is gaining wider attention due to its increasing incidence worldwide. Achalasia due to chagasic megaesophagus (CM), a complication of this disease, is a known-yet, poorly understood-etiological factor for esophageal squamous cell carcinoma (ESCC) development. In this study, we aimed to perform the analysis of TP53 mutations in a series of Brazilian patients with ESCC that developed in the context CM (ESCC/CM), and to compare with the TP53 mutation profile of patients with benign CM and patients with nonchagasic ESCC. Additionally, we intended to correlate the TP53 mutation results with patient's clinical pathological features. By polymerase chain reaction (PCR) followed by direct sequencing of the hotspot regions of TP53 (exon 5 to 8), we found that TP53 mutations were present in 40.6% (13/32) of the ESCC/CM group, 45% (18/40) of the nonchagasic ESCC group, and in only 3% (1/33) of the benign CM group. Missense mutations were the most common in the three groups, yet, the type and mutated exon mutation varied significantly among the groups. Clinically, the groups exhibited distinct features, with both cancer groups (ESCC and ESCC/CM) been significantly associated higher consumption of alcohol and tobacco, older age, worse Karnofsky performance status, poor outcome than the patients with benign CM. No significant association was found between TP53 mutation profile and clinical-pathological features in any of the three groups. We describe first the time the analysis of TP53 mutations in ESCC that developed in the context of CM, and the observed high frequency of mutations, suggest that TP53 also plays an important role in the tumorigenic process of this unexplored etiological condition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mutational profile of TP53 in esophageal squamous cell carcinoma associated with chagasic megaesophagus

Lacerda¹,

Cruvinel-Carloni²,

Oliveira³

et al. 2017

Diseases of the Esophagus

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“…A study examined cytogenetic alterations in patients with chagasic megaesophagus and observed aneuploidies of chromosomes 7, 11, and 17 in 60% and the deletion of the oncogene p53 in 54.5% of 20 study patients; this might increase the risk of tumor development (Manoel-Caetano et al, 2004). While point mutations in exonic regions of p53 , FHIT (fragile histidine triad gene) and CDKN2A (cyclin-dependent kinase Inhibitor 2A) genes or genomic imbalances were not frequent in chagasic megaesophagus, a silent mutation in exon7 of the FHIT gene and copy numbers of the CDKN2A and CEP9 (C-terminally encoded peptide 9) genes might be involved in esophageal carcinogenesis (SM-C et al, 2009, Bellini et al, 2010). The assumed T. cruzi -related carcinogenesis is most likely due to host genetic factors, and the parasite-host interaction resulting in chronic inflammation in particular tissues (Fig.…”

Section: Paradoxical Dual Impacts Of Chagas Disease In Carcinogenesismentioning

confidence: 99%

Parasite Infection, Carcinogenesis and Human Malignancy

et al. 2017

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Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in areas holoendemic for malaria. The initiation of Plasmodium falciparum related endemic Burkitt lymphoma requires additional transforming events induced by the Epstein-Barr virus. Observations suggest that Strongyloides stercoralis may be a relevant co-factor in HTLV-1-related T cell lymphomas. This review provides an overview of the mechanisms of parasitic infection-induced carcinogenicity.

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“…Chagas' disease comprises three phases: an acute phase, usually asymptomatic, a long silent period and finally some patients develop a chronic disease, in which the disease becomes evident with the appearance of cardiac dysfunction, and enlargement of some organs (colon and esophagus, 6-7%) (Bellini et al, 2010). Despite the intense efforts made to develop efficient antiparasitic drugs, an effective treatment for Chagas' disease is still lacking.…”

Section: Introductionmentioning

confidence: 99%