Position paper: Challenges and specific strategies for constitutional mismatch repair deficiency syndrome in low-resource settings.

Rejin Kebudi, Nisreen Amayiri, Malak Abedalthagafi, Asım Noor Rana, Salman Kirmani, Naureen Musthaq, Zakiya Al Lamki, Jamila El Houdzi, Hulya Yazici, Shahenda El-Naggar, Melissa Edwards, Vanessa J Bianchi, Carol Durno, Uri Tabori, Eric Bouffet

Journal: Pediatric blood & cancer 2020;67(8):e28309

PMID: 32472748

Full Text on Ovid Technologies, Inc. View on PubMed

Abstract

Germline biallelic mutations in one of the mismatch repair genes, mutS homolog 2, mutS homolog 6, mutL homolog 1, or postmeiotic segregation increased 2, result in one of the most aggressive cancer syndromes in humans termed as constitutional mismatch repair deficiency (CMMRD). Individuals with CMMRD are affected with multiple tumors arising from multiple organs during childhood, and these individuals rarely reach adulthood without specific interventions. The most common tumors observed are central nervous system, hematological, and gastrointestinal malignancies. The incidence of CMMRD is expected to be high in low-resource settings due to a high rate of consanguinity in these regions, and it is thought to be underrecognized and consequently underdiagnosed. This position paper is therefore important to provide a summary of the current situation, and to highlight the necessity of increasing awareness, diagnostic criteria, and surveillance to improve survival for patients and family members.

Address: Division of Pediatric Hematology-Oncology, Oncology Institute, Istanbul University, Istanbul, Turkey.; Department of Pediatrics, King Hussein Cancer Center, Hematology/Oncology, Amman, Jordan.; Genomics Research Department, Saudi Human Genome Project, King Fahad Medical City, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.; Department of Pediatrics, Division of Hematology-Oncology, Dubai Hospital, Dubai, UAE.; Department of Pediatrics & Child Health, Aga Khan University, Karachi, Pakistan.; Department of Pharmaceutical Sciences, M.M. College of Pharmacy, M.M. University, Mullana, Ambala, Haryana, India.; College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman.; Hematology and Pediatric Oncology Unit, Centre d'Oncologie et d'Hematologie, Mohammed VI University Hospital, Marrakech, Morocco.; Division of Cancer Genetics, Oncology Institute, Istanbul University, Istanbul, Turkey.; Tumor Biology Research Program, Department of Research, Basic Research Unit, Children's Cancer Hospital in Egypt 57357, Cairo, Egypt.; Division of Hematology-Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada.; The Zane Cohen Center, Mount Sinai Hospital, Toronto, Canada.; Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.

DOI: 10.1002/pbc.28309

Link outs

Free resources

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-NF1-1

Subscription / membership required

Full Text Sources:

MeSH Terms: Colorectal Neoplasms, Hereditary Nonpolyposis, DNA Mismatch Repair, Genes, Neoplasm, Germ-Line Mutation, Humans, Incidence, Neoplasm Proteins