Epigenetics is the study of heritable changes in gene expression that do not involve changes to the underlying DNA sequence. It is a change in phenotype without changing in genotype which in turn affects how cellsread the genes. The epigenetic change is a regular occurrence but can also be influenced by several factors including age, environment, lifestyle, and disease state. It may have damaging effects that result in diseases like cancer. At least three systems including DNA methylation, histone modification and RNA-associated gene silencing are currently considered to initiate and sustain epigenetic change. New and ongoing research is continuously uncovering the role of epigenetics in a variety of diseases including in childhood solid cancer such as Ewing sarcoma, neuroblastoma, Wilms tumours, brain tumours and rhabdomyosarcoma. A better understanding of epigenetic changes in childhood cancers can guide towards future therapy and diagnosis.
Hamartomatous polyps of the tonsil are very rare. They have been described using various terms such as a lymphangiomatous polyp, lymphangiectatic fibrous polyp, lipomatous polyp or pedunculated tonsil, thus the actual incidence is difficult to be quantified. We present a case of hamartomatous polyp of the palatine tonsil in a 30-year-old female presented with recurent tonsillitis. Histopathological examination of the resected tonsils showed features of chronic tonsilitis with incidental finding of hamartomatous polyp characterized by a polypoidal tissue covered by stratified squamous epithelium and composed of thin-walled blood vessels, lymphatic channels, fibrofatty tissues, seromucinous glands and striated muscle fibres. An unusual incidental histopathological finding of a rare condition has been discussed along with the review of literature.
Colorectal cancer (CRC) is one of the most common cancer worldwide with approximately 2 to 5% of all colon cancers are associated with well-defined hereditary factors. Hereditary nonpolyposis colorectal cancer (Hereditary Nonpolyposis Colorectal Cancer), also known as Lynch syndrome (LS), is the most common form of hereditary CRC characterized by an early age of onset and follows the autosomal dominant inheritance pattern. HNPCC is caused by the alteration in four mismatch repair (MMR) genes. Immunohistochemistry (IHC) and microsatellite instability (MSI) testing, followed by conventional Sanger sequencing reliably identify the majority of mutations. However, methods to identify other underlying variants or genomic rearrangements of HNPCC have emerged. In addition to the clinical characterization and evaluation of HNPCC patients, the implementation of screening strategies for both affected and unaffected CRC patients together with the accelerated advancement in molecular testing methods will shed light on a more comprehensive detection of HNPCC. In this review, the approaches for the selection of high-risk HNPCC and molecular testing performed over the past few years are discussed.
Breast cancer in young pregnancy is a breast cancer diagnosed in a young lady at the age of less than 30 years old during pregnancy. Diagnosis and treatment of breast cancer during pregnancy are challenging as both maternal and fetal outcome must be considered in terms of their short and long-term effects. It requires multidisciplinary treatment. Instead, pregnancy should be preserved whenever possible, while treating the underlying breast cancer. It is important not to compromise the treatment of breast cancer because of the pregnancy. The overall therapeutic concept basically depends on timing of delivery, staging of the underlying disease, treatment mode and the impacts of treatment recommended as well as foetal outcome in relation to treatment that administered to the mother during pregnancy. We present a case of young pregnant lady at the age of 23 with breast cancer as it is a rare event and the challenges encountered in managing her and to highlight the treatment options for the patient and the baby.
Wan Khairunnisa Wan Juhari, Khairul Bariah Ahmad Amin Noordin, Wan Faiziah Wan Abdul Rahman, Andee Dzulkarnaen Zakaria, Ahmad Shanwani Mohd Sidek, Muhammad Radzi Abu Hassan, et al.
Background: Hereditary nonpolyposis colorectal cancer (HNPCC) also known as Lynch syndrome is commonly caused by genetic alterations in any of the four mismatch repair (MMR) genes; MLH1, MSH2, MSH6 and PMS2. This is the first study aimed to investigate genetic variants in Malay HNPCC families. Methods: Six Malay HNPCC families who fulfilled any of the Bethesda criteria were recruited into this study. A total of 3 ml of blood was withdrawn from each patient in the families. The samples were further analyzed using polymerase chain reaction and direct sequencing of the selected exons of MLH1 and MSH2 genes. Results: Two missense mutations and four single nucleotide polymorphisms (SNPs) were identified in six patients. These variants in the MLH1 and MSH2 genes were identified in four families who met the revised Bethesda guidelines. In two families, no mutation and polymorphism was identified in both the exon and intron of the respective genes. Of the mutations and polymorphisms identified, five have never been reported in Malay HNPCC families before. A missense mutation was detected in exon 5 of the MLH1 gene, c.394G>C (p.Asp132His) and four mutations and polymorphisms were detected in the MSH2 gene; heterozygous c.211+98T>C and c.211+9C>G and homozygous c.211+98T>C and c.211+9C>G, c.367-86A>C and c.382C>G. Conclusion: The results represented a new spectrum of mutations and polymorphisms in the Malay HNPCC families. However, a larger study involving additional families and analysis is required to determine the impact and nature of the identified mutations and polymorphisms.