Inactivating mutations of CASPASE-7 gene in human cancers

Soung, Young Hwa; Lee, Jong Woo; Kim, Hong Sug; Park, Won Sang; Kim, Su Young; Park, Jik Young; Cho, Yong Gu; Kim, Chang Jae; Park, Yong Gyu; Nam, Suk Woo; Jeong, Seong Whan; Kim, Sang Ho; Lee, Jung Young; Yoo, Nam Jin; Lee, Sug Hyung

doi:10.1038/sj.onc.1206727

Cited by 95 publications

(108 citation statements)

References 25 publications

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…An immunohistochemical study has revealed a downregulation of caspase-7 in colon cancer samples compared with that in normal colon mucosa (Palmerini et al, 2001). Soung et al (2003) also observed CASP-7 gene mutations in several types of human solid cancers, including 2 of 98 colon carcinomas (2.0%), 1 of 50 esophageal carcinomas (2.0%), and 1 of 33 head and neck carcinomas (3.0%). To assess the role of CASP-3 and CASP-7 genetic polymorphisms in cancer susceptibility, we conducted a HuGE review and meta-analysis to clarify these associations.…”

Section: Discussionmentioning

confidence: 91%

HuGE systematic review and meta-analysis demonstrate association of CASP-3 and CASP-7 genetic polymorphisms with cancer risk

Yan¹,

Li²,

Zhu³

et al. 2013

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. Genetic variations in the caspase genes CASP-3 and CASP-7 are known to be involved in apoptosis, cytokine maturation, cell growth and differentiation. Polymorphisms of CASP-3 and CASP-7 genes have been increasingly recognized as important regulators in the development of cancer. However, whether there is a specific association is still controversial. Therefore, we made a Human Genome Epidemiology review and meta-analysis to explore the association between polymorphisms of CASP-3 and CASP-7 genes and cancer risk. Based on the inclusion criteria, we examined 9 case-control studies, with a total of 3142 cancer cases and 3670 healthy controls. Meta-analysis results showed that the homozygote (CC) of rs2705897 in the CASP-3 gene is positively associated with cancer susceptibility [odds ratio (OR) = 4.36, 95% confidence interval (CI) = 1.26-15.11, P = 0.02], while the C allele and C carrier (TC+CC) of rs1049216 are negatively associated with cancer risk (OR = 0.81, 95%CI = 0.69-0.95, P = 0.01; OR = 0.78, 95%CI= 0.63-0.97, P = 0.02, respectively). The G allele and G carrier of rs4647603 (A/G) in CASP-3 had positive associations with cancer susceptibility (OR = 1.69, 95%CI = 1.37-2.09, P < 0.001; OR = 1.93, 95%CI = 1.26-2.93, P = 0.002, respectively). The T allele of rs12415607, the G allele and homozygote (GG) of rs2227310, and homozygote (CC) of rs3124740 also had positive associations with cancer risk (OR = 1.18, 95%CI = 1.02-1.37, P = 0.03; OR = 1.17, 95%CI = 1.01-1.34, P = 0.03; OR = 1.34, 95%CI = 1.04-1.74, P = 0.03; OR = 1.30, 95%CI = 1.04-1.63, P = 0.02, respectively). In addition, homozygote (AA) of rs11196418 showed a significant negative association with cancer risk (OR = 0.36, 95%CI = 0.14-0.93, P = 0.03). These meta-analysis results demonstrated that CASP-3 and CASP-7 genetic polymorphisms are involved in the pathogenesis of cancer.

show abstract

Section: Discussionmentioning

confidence: 91%

HuGE systematic review and meta-analysis demonstrate association of CASP-3 and CASP-7 genetic polymorphisms with cancer risk

Yan¹,

Li²,

Zhu³

et al. 2013

Genet. Mol. Res.

View full text Add to dashboard Cite

show abstract

“…Several HRF MCRs contain known CRC genes, including SFRP1 (35), MYC (36), and EGFR (37), as well as REST, a tumor suppressor gene identified in a genetic screen and found to be deleted and/or mutated in CRC (38). In addition, the 10q25.2-10q26.11 HRF MCR spans nine genes, including the WNT signaling mediator TCF7L2/TCF4 (39) and the effector CASP7 (40). Among the remaining 10 HRF MCRs with a total of 65 genes (Tables 1 and 2), there are genes encoding cancer-relevant functions.…”

Section: Resultsmentioning

confidence: 99%

Common and Distinct Genomic Events in Sporadic Colorectal Cancer and Diverse Cancer Types

Martin

Tonon

Sinha³

et al. 2007

Cancer Research

View full text Add to dashboard Cite

Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality, and elucidation of its underlying genetics has advanced diagnostic screening, early detection, and treatment. Because CRC genomes are characterized by numerous non-random chromosomal structural alterations, we sought to delimit regions of recurrent amplifications and deletions in a collection of 42 primary specimens and 37 tumor cell lines derived from chromosomal instability neoplasia and microsatellite instability neoplasia CRC subtypes and to compare the pattern of genomic aberrations in CRC with those in other cancers. Application of oligomer-based arraycomparative genome hybridization and custom analytic tools identified 50 minimal common regions (MCRs) of copy number alterations, 28 amplifications, and 22 deletions. Fifteen were highly recurrent and focal (<12 genes) MCRs, five of them harboring known CRC genes including EGFR and MYC with the remaining 10 containing a total of 65 resident genes with established links to cancer. Furthermore, comparisons of these delimited genomic profiles revealed that 22 of the 50 CRC MCRs are also present in lung cancer, glioblastoma, and/or multiple myeloma. Among 22 shared MCRs, nine do not contain genes previously shown genetically altered in cancer, whereas the remaining 13 harbor 35 known cancer genes, of which only 14 have been linked to CRC pathogenesis. Together, these observations point to the existence of many yet-to-be discovered cancer genes driving CRC development, as well as other human cancers, and show the utility of highresolution copy number analysis in the identification of genetic events common and specific to the development of various tumor types. [Cancer Res 2007;67(22):10736-43]

show abstract

“…When these tumor-derived caspase-7 mutants were expressed in 293 T cells, apoptosis was reduced compared with controls. 81 Moreover, immunohistochemistry analysis showed downregulation of caspase-7 and -9 in colon cancer samples compared with normal mucosa from the same tissue section (Table 1). No changes in the expression of caspase-8 were detected in these tumor samples.…”

Section: Caspases and Cancer M Olsson And B Zhivotovskymentioning

confidence: 98%

Caspases and cancer

2011

View full text Add to dashboard Cite

Evasion of apoptosis is considered to be one of the hallmarks of human cancers. This cell death modality is executed by caspases and several upstream regulatory factors, which direct their proteolytic activity, have been defined as either tumor suppressors or oncogenes. Often these regulatory factors, in addition to being potent apoptosis inducers, function in cell survival or repair signaling pathways in response to cellular stress. Thus, loss of function in a distinct regulatory mechanism does not necessarily mean that tumor formation is due to apoptosis malfunction resulting from insufficient caspase activation. Although each caspase has been assigned a distinct role in apoptosis, some redundancy with respect to their regulatory functions and substrate recognition is evident. Jointly, these proteases could be considered to possess solid tumor suppressor function, but what is the evidence that deregulation of specific caspases per se induces inappropriate cell survival, leading to enhanced tumorigenic potential? This question will be addressed in this review, which covers basic molecular mechanisms derived from in vitro analyses and emphasizes new insights that have emerged from in vivo and clinical studies. In organisms, excess cells during development, as well as potentially harmful cells resulting from pathophysiological conditions, are eliminated by various cell death modalities. Among them, apoptosis is the most investigated, and almost 40 years ago, it was described as a major defense strategy that prevents cells from acquiring tumorigenic potential. 1 This suicide mechanism is controlled by multiple and interrelated pathways ensuring that caspases, the proteolytic initiators and executioners of apoptosis, are triggered only in cells requiring termination. There is overwhelming experimental evidence supporting the idea that disturbances in the regulation of caspase activation are central for the avoidance of cancer cell death, both in vitro and in vivo. However, what evidences suggest that caspases per se act as tumor suppressors? It was reported that cells do not necessarily undergo caspaseindependent cell death in the absence of active caspases, but may instead survive insult and even promote clonogenic tumor growth. 2 Yet, it was unclear which individual caspases could fulfill this function. Recently, certain initiator caspases have been suggested as putative tumor suppressor genes. 3,4 This review is focusing on caspases and their role in tumor suppression, and emphasizing new evidences that have emerged from in vivo observations and clinical material, taking into consideration supporting in vitro data that has enlightened basic molecular mechanisms. CaspasesClassification of human caspases is based either on their function, the size of their pro-domain or cleavage specificity.Considering the first criteria, caspase-1, -4 and -5 belong to the group I (inflammatory) caspases that are involved in cytokine maturation. These proteases are primarily associated with the innate immunity against pathogens an...

show abstract

Inactivating mutations of CASPASE-7 gene in human cancers

Cited by 95 publications

References 25 publications

HuGE systematic review and meta-analysis demonstrate association of CASP-3 and CASP-7 genetic polymorphisms with cancer risk

HuGE systematic review and meta-analysis demonstrate association of CASP-3 and CASP-7 genetic polymorphisms with cancer risk

Common and Distinct Genomic Events in Sporadic Colorectal Cancer and Diverse Cancer Types

Caspases and cancer

Contact Info

Product

Resources

About