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K nudson's hypothesis revisited in I ndian retinoblastoma patients
Author(s) -
Gaikwad Namrata,
Vanniarajan Ayyasamy,
Husain Akram,
Jeyaram Illaiyaraja,
Thirumalairaj Kannan,
Santhi Radhakrishnan,
Muthukkaruppan Veerappan,
Kim Usha
Publication year - 2015
Publication title -
asia‐pacific journal of clinical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 29
eISSN - 1743-7563
pISSN - 1743-7555
DOI - 10.1111/ajco.12401
Subject(s) - retinoblastoma , medicine , germline mutation , malignancy , germline , family history , oncology , mutation , genetics , biology , gene
Aim Retinoblastoma (RB) is the most common primary intraocular malignancy affecting children under 5 years of age. This study aims to correlate the clinical parameters with RB 1 mutation in the light of K nudson's two‐hit hypothesis in I ndian RB patients. Methods We analyzed the clinical details of 73 RB patients visiting A ravind E ye H ospital, M adurai, I ndia, between J anuary and O ctober 2012. Data on gender, presenting age and sign, laterality, number of tumors in each eye and family history were collected. A semi log plot was derived based on K nudson's two‐hit hypothesis. Genetic analysis of RB 1 was carried out to identify the two hits. Results The mean age at diagnosis for unilateral and bilateral cases was 24.0 ± 15.1 and 9.8 ± 11.5 months, respectively. Familial RB was seen in 13 (17.8%) patients of whom 11 were bilateral. Multiple tumors were observed more frequently in bilateral than in unilateral cases. All unilateral and bilateral patients followed the two‐hit and one‐hit curves, respectively, confirming K nudson's hypothesis in I ndian patients. Genetic analysis identified two somatic mutations in tumor samples of sporadic unilateral cases. Among the two bilateral patients, one received the first hit from her father and the other patient developed a de novo germline mutation during early development. Conclusion The two‐hit hypothesis has been reestablished in I ndian patients. Genetic analysis of tumor samples has also complemented the statistical analysis to reaffirm the two hits in tumor development.