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High frequency of mismatch repair deficiency among pediatric high grade gliomas in Jordan.
- Source :
-
International journal of cancer [Int J Cancer] 2016 Jan 15; Vol. 138 (2), pp. 380-5. Date of Electronic Publication: 2015 Aug 21. - Publication Year :
- 2016
-
Abstract
- Biallelic mismatch repair deficiency (bMMRD) is a cancer predisposition syndrome affecting primarily individuals from consanguinous families resulting in multiple childhood cancers including high grade gliomas (HGG). This is the first study to assess the prevalence of bMMRD among patients with HGG in countries where consanguinity is high. We collected molecular and clinical information on all children diagnosed with HGG and supratentorial primitive neuroectodermal tumors (sPNET) between 2003 and 2013 at King Hussein Cancer Center, Jordan. Comparison was made to a similar cohort from Toronto. Clinical data regarding presence of café au lait macules(CAL), family history of cancer, consanguinity, pathology and treatment were collected. Tumors were centrally reviewed and tested for MMRD by immunohistochemistry of the corresponding proteins. Forty-two patients fulfilled the inclusion criteria, including 36 with HGG. MMRD was observed in 39% of HGG of whom 79% also lost MMR staining in the corresponding normal cells suggestive of bMMRD. P53 dysfunction was highly enriched in MMR deficient tumors (p = 0.0003).The frequency of MMRD was significantly lower in Toronto cohort (23%, p = 0.03). Both evidence of CAL and consanguinity correlated with bMMRD (p = 0.005 and 0.05,respectively) but family history of cancer didn't. HGG with all three bMMRD risk factors had evidence of MMRD and all children affected by multiple bMMRD related cancers had identical gene loss by immunohistochemical staining. In Jordan, the frequency of clinical and immunohistochemical alterations suggestive of bMMRD in pediatric HGG is high. Genetic testing will enable appropriate counseling and cancer screening to improve survival of these patients.<br /> (© 2015 UICC.)
- Subjects :
- Adolescent
Brain Neoplasms epidemiology
Brain Neoplasms mortality
Brain Neoplasms pathology
Child
Child, Preschool
Female
Glioma mortality
Glioma pathology
Humans
Immunohistochemistry
Infant
Infant, Newborn
Jordan
Kaplan-Meier Estimate
Male
Neoplasm Grading
Retrospective Studies
Risk Factors
Brain Neoplasms genetics
Colorectal Neoplasms epidemiology
DNA Mismatch Repair genetics
Glioma genetics
Neoplastic Syndromes, Hereditary epidemiology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0215
- Volume :
- 138
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 26293621
- Full Text :
- https://doi.org/10.1002/ijc.29724