Microsatellite instability, prognosis and metastasis in gastric cancers from a low-risk population

Schneider, Barbara; Bravo, Juan Carlos; Roa, Juan Carlos; Roa, Iván; Kim, M.C.; Lee, K.M.; Plaisance, Kerry T.; McBride, Charles M.; Mera, Robertino

doi:10.1002/1097-0215(20000920)89:5<444::aid-ijc8>3.0.co;2-f

Cited by 54 publications

(70 citation statements)

References 40 publications

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“…Consequently, the loss of APAF-1 gene function leads to defects in the execution of apoptotic programmed cell death and may account for cellular resistance to chemo-, radio-, and immunotherapy. APAF-1 is located at chromosome loci 12q23 , and frequent AI in the 12q22-23 region has been reported in melanomas (Soengas et al, 2001;Fujimoto et al, 2004), male germ cell tumors (Murty et al, 1996), and pancreatic (Kimura et al, 1998;Yatsuoka et al, 2000), ovarian (Hatta et al, 1997) and gastric carcinomas (Schneider et al, 2003). In melanomas, AI is associated with a reduction of APAF-1 mRNA expression levels (Soengas et al, 2001;Fujimoto et al, 2004), and AI in the 12q22-23 region is related to poor prognosis of patients with American Joint Committee on Cancer (AJCC) stage III/IV melanoma .…”

Section: Introductionmentioning

confidence: 99%

Allelic imbalance of APAF-1 locus at 12q23 is related to progression of colorectal carcinoma

et al. 2004

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APAF-1 gene, located at chromosome locus 12q23, is a key factor in the mitochondrial apoptotic pathway downstream of p53, and is a potential tumor suppressor gene. We hypothesized that APAF-1 gene dysfunction due to allelic imbalance (AI) contributes to the development and progression of colorectal carcinoma (CRC). AI at APAF-1 locus and microsatellite instability (MIN) in CRCs and adenomas were assessed by multiple microsatellite markers. The frequency of AI significantly increased with tumor progression; 0 of 33 (0%) adenomas, 14 of 49 (29%) primary CRCs, and 18 of 34 (53%) liver metastases had AI. A total of 12 metastases were matched with corresponding primary CRCs; in 11 of 12 (92%) pairs, the metastasis had same AI status as the corresponding primary tumor. APAF-1 mRNA transcription level was significantly decreased with AI in liver metastases (P ¼ 0.009). Promoter hypermethylation was found in three of 35 (9%) primary CRCs and one of 15 (7%) liver metastases by methylation-specific PCR but was not correlated with AI. MIN was observed in 11 of 49 (23%) primary CRCs and was a favorable prognostic factor. Our results suggest that APAF-1 gene haploinsufficiency caused by AI increases with tumor progression, and relates to hepatic metastasis.

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Section: Introductionmentioning

confidence: 99%

Allelic imbalance of APAF-1 locus at 12q23 is related to progression of colorectal carcinoma

et al. 2004

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“…50,51,56 Females were found to have MSI-H tumors more frequently than males. Most studies have not reported a gender difference associated with MSI-H status, 41,50,51,55 although the data published by Olivera and colleagues, 54 Ohmura and colleagues, 42 and Ottini and colleagues 43 seems to show a similar trend to what we have observed. This may be a sample size issue because MSI-H tumors represent only a small portion of the overall tumors studied.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism generating MSI-H tumors is thought to be different from tumors with proficient mismatch repair, so these tumors were identified and evaluated separately. An article by Schneider and colleagues 50 suggested that MSI-L tumors might be phenotypically distinct from MSS tumors. No differences in survival were found either when the three categories of MSI (MSI-H, MSI-L, and MSS) were treated as separate groups or when the MSS and MSI-L subclasses were combined into a larger group, which was then compared to MSI-H.…”

Section: Discussionmentioning

confidence: 99%

“…52,53,55,61 Moreover, MSI-H tumors are thought to be of a less aggressive nature, possibly accounting for their presentation at a lower stage and better survival rate. 41,44,50,53,55 A subclone existing within a tumor that has not lost its MMR function might be more aggressive and exhibit clonal dominance regarding growth within the murine environment compared to MMR-deficient clones. Overall, our results, in agreement with others in the literature, demonstrate xenografted tumors to be very reliable in exhibiting global molecular alterations consistent with the primary tumor that might otherwise go undetected because of normal stromal content.…”

Section: Discussionmentioning

confidence: 99%

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Allelic Imbalance of 8p Indicates Poor Survival in Gastric Cancer

French

Petroni

Thibideau

et al. 2004

The Journal of Molecular Diagnostics

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Gastric cancer is a common tumor worldwide and a tremendous health burden. However, the underlying mechanisms of tumorigenesis in this cancer's development are primarily undefined. Allelic imbalance (AI) of 8p has been reported in many cancers, yet, the target(s) of alteration and the importance of allelic imbalance on this chromosomal arm in gastric carcinoma development remained to be characterized. Our findings confirmed a high rate of AI on 8p in gastric cancers. Moreover, we demonstrated that AI on 8p, either overall or at marker D8S560, was associated with poorer survival in patients with gastric cancer. Finally, gastric cancers with a high rate of microsatellite instability were significantly associated with noncardia tumors and with female gender.

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“…La microdisección fue desarrollada utilizando un aparato de microdisección Láser Pixcell I (Arcturus Engineering Inc., Mountainview, CA) equipado con una fuente de bajo poder (50-mW) con un rayo láser 27,28 . La microdisección por captura láser (LCM) fue utilizada para seleccionar células desde secciones no cubiertas con cubreobjeto y teñidas con hematoxilina.…”

Section: Microdisección Y Extracción De Adnunclassified

Alteraciones genéticas en gastritis crónica: Estudio de inestabilidad microsatelital y pérdida de la heterocigocidad

Roa

Villaseca

et al. 2003

Rev. méd. Chile

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Microsatellite instability, prognosis and metastasis in gastric cancers from a low-risk population

Cited by 54 publications

References 40 publications

Allelic imbalance of APAF-1 locus at 12q23 is related to progression of colorectal carcinoma

Allelic imbalance of APAF-1 locus at 12q23 is related to progression of colorectal carcinoma

Allelic Imbalance of 8p Indicates Poor Survival in Gastric Cancer

Alteraciones genéticas en gastritis crónica: Estudio de inestabilidad microsatelital y pérdida de la heterocigocidad

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