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Fulltext Cytogenetic abnormalities at diagnosis and during follow up in multiple myeloma patients and their prognostic implications - a preliminary report

Eva Foong, Ismail Siti-Mariam, Ramli Norhidayah, Abu Bakar Zulaikha, Mat Zin Nik-Mohd-Zulfikri, Mohd Nawi Nurul-Alia, et al.

Malaysian Journal of Medicine and Health Sciences, 2020;16(4):108-117.
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Introduction: Multiple myeloma (MM) is characterized by genomic instability and cytogenetic abnormalities (CAs). The variation in rates of treatment response and overall survival is thought to arise from multiple genomic events that result in tumour development and progression. This study investigated CAs among the newly diagnosed MM (NDMM) patients at diagnosis and during follow-up and subsequently to assess their prognostic significance. Meth- ods: This is a prospective cohort study where bone marrow (BM) samples of 16 NDMM patients were collected at diagnosis and during follow up and subjected to conventional cytogenetic analysis (CCA) and interphase fluores- cence in situ hybridization (iFISH) analyses using standard procedures. Spectral karyotyping was performed on a selected patient who showed complex karyotype (CK) pattern on CCA. Results: Clonal abnormalities were identified in 56.3% of analysis by karyotyping and 68.8% by combination of karyotyping and iFISH. CCA showed normal diploid, hypodiploid and hyperdiploid karyotypes, whereas iFISH analysis could detect various IGH translocations involving 14q32 region, del(13q14) and del(17p13). Significant associations were observed between patients with complex karyotypes and abnormal karyotypes. Patients who had a CK or showed an abnormal CCA and iFISH results were associated with worse survival (p=0.011 and p=0.034 respectively). Structural abnormalities were found to be more common among hyperdiploid MM patients (p=0.001). Cytogenetic evolution was seen in the follow-up of BM cytogenetics. Conclusion: Karyotyping and iFISH are valuable assets in detecting prognostically relevant genomic abnormalities. The presence of cytogenetic evolution demonstrated the value of cytogenetics in monitoring treatment response and in management of MM.
Fulltext Pericentric Inversion of Chromosome 9 in Twins With Cyclopia: A Rare Entity

Nik Lah NAZ, Taib F, Mohamad Zon E, Engku Ismail EH, Annuar AA

Cureus, 2023 Feb;15(2):e34562.
PMID: 36743908 DOI: 10.7759/cureus.34562

Pericentric inversion of chromosome 9 (inv(9)) is one of the most common variants seen in a normal human karyotype that occurs during meiosis. Despite being categorized as a normal variant, some studies using classical cytogenetics have recently shown that inv(9) could be associated with azoospermia, congenital anomalies, growth retardation, and rarely with abnormal karyotype. However, there is no reported association with cyclopia. Interestingly this genetic variant involves twin fetuses. A 36-year-old multiparous lady with dichorionic diamniotic twin pregnancy presented to the fetomaternal unit with fetal growth restriction at 34 weeks of gestation. An ultrasound scan revealed both have microcephaly, fisting hands, holoprosencephaly, and proboscis suspicious of Patau syndrome. Amniocentesis was not issued due to late pregnancy and guarded prognosis. The mother presented with pre-eclampsia at 35 weeks of gestation. The pregnancy managed to prolong up to 36 weeks after which caesarean section was performed due to the leading twin being in a transverse lie. Two baby twin girls were born 3 minutes apart with microcephaly and cyclops appearance. Chromosomal analysis of both twins revealed similar karyotypes of 46, XX, inv(9)(p11,q13). Pericentric inversion of chromosome 9 is regarded as a normal chromosomal variation in the general population, but in twins with cyclops is considered rare. Early referral to a tertiary hospital for twin management is highly required. It may identify fetuses with such abnormalities and counsel the parents with appropriate management.
Chromosome Translocation t(6; 14) With Different Phenotypes and Segregation Patterns: A Report of Two Cases

Ankathil R, Zakaria WNA, Hamid MR, Ismail SM, Mohd Yunus N, Annuar AA, et al.

Cureus, 2024 Sep;16(9):e68402.
PMID: 39360045 DOI: 10.7759/cureus.68402

Chromosomal rearrangement can disrupt gene function by interfering with coding sequences or their regulatory regions. The breakpoint in these rearrangements can pinpoint the disease-related gene's location. This paper presents two rare cases of chromosomal rearrangement involving chromosome 6 (6p24-25) and chromosome 14 (14q22-23). The first case involves a girl with hearing impairment, inheriting a balanced translocation of chromosomes 6 and 14 from her father. The second case describes a dysmorphic baby boy with congenital bilateral choanal atresia and a tertiary trisomy, involving a translocation between chromosome 6 (6p24) and chromosome 14 (14q22), resulting in a derivative chromosome (14) in addition to the normal complement of chromosomes 6 and 14. The boy's mother had a history of four recurrent miscarriages. However, the origin of this tertiary trisomy in the second case presented could not be delineated because the parents did not consent and declined their blood samples for karyotyping. Parental karyotyping and chromosomal analysis are crucial for investigating recurrent miscarriages, identifying genetic causes, guiding reproductive decisions, and improving successful pregnancy outcomes for affected couples.
Fulltext Impact of Fas/Fasl Gene Polymorphisms on Susceptibility Risk and Imatinib Mesylate Treatment Response in Chronic Myeloid Leukaemia Patients

Annuar AA, Ankathil R, Mohd Yunus N, Husin A, Ab Rajab NS, Abdul Aziz AA, et al.

Asian Pac J Cancer Prev, 2021 Feb 01;22(2):565-571.
PMID: 33639675 DOI: 10.31557/APJCP.2021.22.2.565

BACKGROUND: The FAS mediated apoptosis pathway involving the FAS and FASL genes plays a crucial role in the regulation of apoptotic cell death and imatinib mesylate (IM) mechanism of action. Promoter polymorphisms FAS-670 A>G and FAS-844 T>C which alter the transcriptional activity of these genes may grant a risk to develop cancer and revamp the drug activities towards the cancer cell. We investigated the association of these two polymorphisms with the susceptibility risk and IM treatment response in Malaysian chronic myeloid leukaemia (CML) patients.
METHODS: This is a retrospective study, which included 93 CML patients and 98 controls. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method was used to genotype the FAS and FASL polymorphisms. Data nanlysis was done using SPSS Version 22. The associations of the genotypes with susceptibility risk and IM response in CML patients were assessed by means of logistic regression analysis and deriving odds ratio with 95% CI.
RESULTS: We observed a significant association between FASL-844T>C polymorphism and CML susceptibility risk and IM response. Variant C allele and FASL-844 CC variant genotype carriers had significantly higher risk for CML susceptibility (OR 1.756, CI 1.163-2.652, p=0.007 and OR 2.261, CI 1.013-5.047, p=0.047 respectively). Conversely, the heterozygous genotype FASL-844 TC conferred lower risk for CML susceptibility (OR 0.379, CI 0.176-0.816, p=0.013). The heterozygous and homozygous variant genotypes and variant C alleles were found to confer a lower risk for the development of IM resistance with OR 0.129 (95% CI: 0.034-0.489 p=0.003), OR 0.257 (95% CI: 0.081-0.818, p=0.021), and OR 0.486 (95% CI: 0.262-0.899, p=0.021) respectively. We also found that FAS-670 A>G polymorphism was not associated with CML susceptibility risk or IM response.
CONCLUSION: The genetic polymorphism FASL-844 T>C may contribute to the CML susceptibility risk and also IM treatment response in CML patients. Accodringly, it may be useful as a biomarker for predicting CML susceptibility risk and IM resistance.