Clinical and Prognostic Features in a Young Adult Patient with de novo Myelodysplastic Syndrome presenting t(11;16) (q23; q24)

hematopoietic clonal neoplasms. MDS occurs mainly in elderly patients. KMT2A rearrangements (KMT2A-r) are rare in MDS, so little is known about their prognostic value. The present study describes the clinical characteristics of a young adult patient diagnosed with MDS-EB-2, presenting the t(11;16)(q23;q24). The Decitabine treatment was initiated since no matching donor was found. The patient showed improved anemia and thrombocytopenia. However, he still had severe neutropenia and clonal chromosomal alteration. Two months after the fifth cycle of Decitabine, the patient presented a worsening of the clinical parameters with increased blast and evolution to AML. He was treated with intensification chemotherapy, but despite all efforts, the patient evolved to death. Treatment refractoriness and leukemia transformation suggest that t(11;16)(q23;q24) with KMT2A-r was associated with poor prognosis. This study reinforces the importance of characterizing new chromosomal alterations and their impact on prognosis in MDS.

Transmission Jeopardy of Adenomatosis Polyposis Coli and Methylenetetrahydrofolate Reductase in Colorectal Cancer

Colorectal cancer (CRC) is one of the globally prevalent and virulent types of cancer with a distinct alteration in chromosomes. Often, any alterations in the adenomatosis polyposis coli (APC), a tumor suppressor gene, and methylenetetrahydrofolate reductase (MTHFR) gene are related to surmise colorectal cancer significantly. In this study, we have investigated chromosomal and gene variants to discern a new-fangled gene and its expression in the southern populations of India by primarily spotting the screened APC and MTHFR variants in CRC patients. An equal number of CRC patients and healthy control subjects ( n = 65 ) were evaluated to observe a chromosomal alteration in the concerted and singular manner for APC and MTHFR genotypes using standard protocols. The increasing prognosis was observed in persons with higher alcoholism and smoking ( P < 0.05 ) with frequent alterations in chromosomes 1, 5, 12, 13, 15, 17, 18, 21, and 22. The APC Asp 1822Val and MTHFR C677T genotypes provided significant results, while the variant alleles of this polymorphism were linked with an elevated risk of CRC. Chromosomal alterations can be the major cause in inducing carcinogenic outcomes in CRCs and can drive to extreme pathological states.

Clinical and neurological findings of a patient with a complex chromosome 5 alteration

Context: Inversion-duplication-deletion (invdupdel) involving the short arm of chromosome 5 is considered a complex and extremely rare alteration. Case report: A female patient was born prematurely at 32 weeks and was delivered by cesarean section, weighing 2,086 grams, with an Apgar score in the fifth minute of 7. After birth, she needed invasive mechanical ventilation. A nasofibrolaryngoscopy was performed, which revealed the rear projection of the tongue base. The speech-language evaluation showed a swallowing disorder. The patient needed to be tracheostomized and evolved with episodes of cardiorespiratory arrest. A zone 2 of immaturity was identified in both eyes. Then, gastroesophageal reflux was also diagnosed. Cerebral ultrasound showed moderate lateral ventricles dilation. High resolution GTG-banding karyotype identified an inverted and partial duplication of the chromosome’s 5 short arm, with a probable deletion of its distal segment: 46,XX,invdup(5) (p13.3->p15.33:: p15.33->qter) [23]. The parents’ karyotype was normal. At 2 months, the patient had dolichocephaly; bitemporal narrowing; hypertelorism; and down slanting palpebral fissures with blepharophimosis; low-set and posteriorly rotated ears; leftover skin at neck and bilateral plantar creases between the first, second and third toes. Conclusions: Invdupdel of the short arm of chromosome 5 is a very rare chromosomal alteration. Neurological findings seem to be part of its clinical manifestations, especially dilated lateral ventricles. More reports will be essential for understanding its clinical spectrum.

CLONAL HEMATOPOIESIS IN A CENTENARIAN COHORT

Mosaicism, the presence of two or more genotypically or karyotypically distinct populations of cells in a single individual, plays an important role in human disease. Mosaicism can result in mutations and/or chromosomal alterations such as loss, gain, or copy-number neutral loss of heterozygosity. Clonal mosaicism and its relationship to aging and cancer, has been previously studied, and earlier work suggests that clonal mosaicism tends to increase with age. The aim of our research is to use genotype data of centenarians to explore the relationship between extreme longevity and mosaic chromosomal alterations (mCAs). To this end, we analyzed genome-wide genotypes from blood-derived DNA of 338 individuals from the New England Centenarian Study. The participants in this dataset ranged from 45 to 112 years of age. For the detection of mCA events, we used MoChA (https://github.com/freeseek/mocha), a bcftools extension, that predicts mCAs based on B-allele frequency (BAF) and log2 intensity(R) ratio (LRR), and uses long-range phase information to increase sensitivity. Chromosomal alteration events, including whole chromosome events, were detected in 180 out of the 338 individuals. A total of 165 duplications, 97 deletions, and 9 copy-number neutral loss of heterozygosity were detected. Additionally, there were 42 events whose copy number state could not be determined with high confidence. 236 events out of the 313 were detected in individuals aged 100 and older. Our analysis of chromosomal alteration frequency by age indicates that, within centenarians, the proportion of individuals with mCAs significantly decreases with increased age (p &lt; 0.05, correlation -0.73).