HNPCC-associated small bowel cancer: Clinical and molecular characteristics

Schulmann, Karsten; Brasch, Frank; Kunstmann, Erdmute; Engel, Christoph; Pagenstecher, Constanze; Vogelsang, H.; Krüger, Stefan; Vogel, Tilman; Knaebel, H. P.; Rüschoff, Josef; Hahn, Stephan A.; Knebel‐Doeberitz, Magnus von; Möeslein, Gabriela; Meltzer, Stephen J.; Schackert, Hans K.; Tympner, Christiane; Mangold, Elisabeth; Schmiegel, Wolff

doi:10.1053/j.gastro.2004.12.051

Cited by 173 publications

(126 citation statements)

References 50 publications

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“…The mean age at diagnosis of SBC in our study population was 48 years, which is consistent with the age reported in two previous studies (13,17), but is f10 years older than the age of diagnosis reported for German patients (16). We found that SBCs occurred at similar ages at which diagnosis of colorectal cancer and endometrial cancers were made in our HNPCC patients, which is consistent with a previous report (18).…”

Section: Resultssupporting

confidence: 92%

“…Rodriguez-Bigas et al reported 49 SBCs from 42 HNPCC patients, based on a questionnaire mailed to members of the International Collaborative Group on HNPCC, which includes individuals from the United States, the Netherlands, Denmark, Finland, Australia, Italy, Portugal, Canada, and Israel (13). Recently, a study from the German HNPCC Consortium reported 32 SBCs from 31 unrelated HNPCC patients, detailing both the pathologic features and the clinical characteristics (16). Similar to the study by Rodriguez-Bigas et al, the present work was based on a questionnaire mailed to participating centers from 13 countries worldwide.…”

Section: Resultsmentioning

confidence: 99%

“…Although it remains to be defined, correlation between biallelic mutations and very young cancer might be probable. Studies have shown that both sporadic (20) and HNPCCassociated (13,16) SBCs are more common in males than females, with the latter showing a reported 3:1 ratio of males to females. In the present study, 60% of our enrolled patients were male, yielding a 3:2 ratio of males to females that is relatively consistent with the previous findings.…”

Section: Resultsmentioning

confidence: 99%

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Germ Line Mutations of Mismatch Repair Genes in Hereditary Nonpolyposis Colorectal Cancer Patients with Small Bowel Cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study

Park

Kim

Hong

et al. 2006

Clinical Cancer Research

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Purpose:The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). Experimental Design: A questionnaire was mailed to 55 members of the International Society for Gastrointestinal Hereditary Tumours, requesting information regarding patients with HNPCCassociated SBC and germ line mismatch repair gene mutations. Results: The study population consisted of 85 HNPCC patients with identified mismatch repair gene mutations and SBCs. SBC was the first HNPCC-associated malignancy in 14 of 41 (34.1%) patients for whom a personal history of HNPCC-associated cancers was available. The study population harbored 69 different germ line mismatch repair gene mutations, including 31 mutations in MLH1, 34 in MSH2, 3 in MSH6, and 1in PMS2. We compared the distribution of the mismatch repair mutations in our study population with that in a control group, including all pathogenic mismatch repair mutations of the International Society for Gastrointestinal Hereditary Tumours database (excluding those in our study population). In patients with MSH2 mutations, patients with HNPCC-associated SBCs had fewer mutations in the MutL homologue interaction domain (2.9% versus 19.9%, P = 0.019) but an increased frequency of mutations in codons 626 to 733, a domain that has not previously been associated with a known function, versus the control group (26.5% versus 2.8%, P < 0.001).Conclusions: In HNPCC patients, SBC can be the first and only cancer and may develop as soon as the early teens.The distribution of MSH2 mutations found in patients with HNPCC-associated SBCs significantly differed from that found in the control group (P < 0.001).

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Germ Line Mutations of Mismatch Repair Genes in Hereditary Nonpolyposis Colorectal Cancer Patients with Small Bowel Cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study

Park

Kim

Hong

et al. 2006

Clinical Cancer Research

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“…In addition, patients are at risk of developing a wide range of tumors outside of the colon including but not limited to: endometrial, ovarian, gastric and pancreatic cancer. Patients with HNPCC also have a 3% lifetime risk of developing a brain tumor [115][116][117].…”

Section: Relation To Hereditary Non-polyposis Colorectal Carcinoma (Hmentioning

confidence: 99%

Recent developments in brain tumor predisposing syndromes

2015

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“…AIM2 gene was originally identified by subtractive cDNA selection for association with human melanoma tumorigenicity (15) and only shares 31% protein identity with IFIXa1 (14). The AIM2 gene contains a site of microsatellite instability that results in gene inactivation in 47.6% of colorectal tumors with high microsatellite instability (16). AIM2 gene mutation has also been found in association with gastric and endometrial cancers (17).…”

Section: Introductionmentioning

confidence: 99%

AIM2 suppresses human breast cancer cell proliferation in vitro and mammary tumor growth in a mouse model

Chen

Ou‐Yang

Hung

et al. 2006

Molecular Cancer Therapeutics

123

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IFN-inducible proteins are known to mediate IFN-directed antitumor effects. The human IFN-inducible protein absent in melanoma 2 (AIM2) gene encodes a 39-kDa protein, which contains a 200-amino-acid repeat as a signature of HIN-200 family (hematopoietic IFN-inducible nuclear proteins). Although AIM2 is known to inhibit fibroblast cell growth in vitro, its antitumor activity has not been shown. Here, we showed that AIM2 expression suppressed the proliferation and tumorigenicity of human breast cancer cells, and that AIM2 gene therapy inhibited mammary tumor growth in an orthotopic tumor model. We further showed that AIM2 significantly increased sub-G 1 phase cell population, indicating that AIM2 could induce tumor cell apoptosis. Moreover, AIM2 expression greatly suppressed nuclear factor-KB transcriptional activity and desensitized tumor necrosis factor-A -mediated nuclear factor-KB activation. Together, these results suggest that AIM2 associates with tumor suppression activity and may serve as a potential therapeutic gene for future development of AIM2-based gene therapy for human breast cancer.

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HNPCC-associated small bowel cancer: Clinical and molecular characteristics

Cited by 173 publications

References 50 publications

Germ Line Mutations of Mismatch Repair Genes in Hereditary Nonpolyposis Colorectal Cancer Patients with Small Bowel Cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study

Germ Line Mutations of Mismatch Repair Genes in Hereditary Nonpolyposis Colorectal Cancer Patients with Small Bowel Cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study

Recent developments in brain tumor predisposing syndromes

AIM2 suppresses human breast cancer cell proliferation in vitro and mammary tumor growth in a mouse model

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