Synoptic Abstracts 2024
February 2024
Genome-wide association study and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer
Laskar et al. Ann Oncol. 2024 Feb 24.
Synopsis
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Around the world, more young adults are succumbing to early onset colorectal cancer (EOCRC). Besides known factors, other risk factors causing this cancer are unknown.
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Genome Wide Association Study (GWAS) was used to evaluate 6,176 cases and 65,829 controls from other studies. Twenty-eight risk factors associated with body size and metabolic activity were studied by mendelian randomization (MR).
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The authors found that locations on chromosomes 1 and 4 and non-coding signals in gastrointestinal epithelial tract cells were associated with CRC risk. Moreover, risk for EOCRC increased with increase in body fat, basal metabolic rate, fasting insulin, and alcohol consumption, and low education.
Conclusion
Therefore, this study showed that long-time sleep deprivation can lead to cognitive decline.
Adeno-to-squamous transition drives resistance to KRAS inhibition in LKB1 mutant lung cancer
Synopsis
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Lung cancer is characterized by KRAS mutations. KRAS inhibitors adagrasib and sotorasib reduce tumor progression; however, this treatment eventually results in resistance.
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Resistance developed in mice and organ models (organoids) with KRAS and LKB1 c-mutations due to tumorigenic cellular transformations arising from KRAS inhibitor treatment.
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Therefore, adeno to squamous transition (AST), a type of tumorigenic transformations, corelates with resistance to adagrasib.
Conclusion
AST in lung cancer predicts treatment resistance and provides biomarkers, which can be used to improve lung cancer therapies.
May 2024
Gene Editing for CEP290-Associated Retinal Degeneration
Pierce et al. N Engl J Med. 2024 May 6.
Synopsis
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Early blindness is caused by retinal degeneration due to CEP290 variants such as mutations in intron 26. It can be treated by EDIT-1, a CRISPR-Cas9 gene editing therapy.
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EDIT-101 was injected into the diseased eye of persons with inherited retinal degeneration (12 adults and 2 children). Safety and toxicity were measured primarily. Secondary measures were improvement in vision, retinal sensitivity, and vision-related mobility testing and quality of life.
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The treatment was safe without any dangerous side effects. Vision, retinal sensitivity, and vision-related mobility improved in 64% of treated individuals. The quality of life improved in six of the treated individuals.
Conclusion
This study shows that CRISPR-Cas9 based gene editing such as EDIT-101 is a promising therapy for inherited retinal diseases.
June 2024
HBV integrations reshaping genomic structures promote hepatocellular carcinoma
Qian et al. Gut. 2024 Jun 6.
Synopsis
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The authors investigated the role of unknown hepatitis B virus (HBV) DNA integrations with host DNA in hepatocellular carcinoma (HCC).
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Many HBV genetic integrations were classified by whole genome sequencing and Nanopore long reads in 124 HCCs from all age groups. Tumorigenic genetic integrations were identified in mouse hepatocytes by CRISPR screening.
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HBV integration was common in young persons, and increased with high HBV DNA, and TP53 mutations. Additionally, HBV integration in chromosome 8q was tumorigenic.
Conclusion
HBV can cause tumors by altering specific chromosomes, thereby speeding the onset of HCC.
Aug 2024
Hypothermic oxygenated perfusion of the donor heart in heart transplantation: the short-term outcome from a randomised, controlled, open-label, multicentre clinical trial
Rega F et al. Lancet. 2024 Aug 17.
Synopsis
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For heart transplantation, donor hearts are preserved by static cold storage (SCS) which reduces survival because of poor organ oxygenation and injuries. This study recruited 229 patients aged 18-70 years to evaluate if hypothermic oxygenated machine perfusion (HOPE) is a better and safer method for preserving donor hearts.
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There was a 44% reduction in risk (p=0.059) when hearts preserved by HOPE were transplanted. Compared to 31 patients (30%) in the SCS group, 19 (19%) patients in the HOPE group experienced death or a heart-disease-related event.
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More major cardiac events occurred in 33 (32%) patients in the SCS group than in 18 (18%) patients in the HOPE group.
Conclusion
Hearts preserved by HOPE improved survival in transplant patients than those preserved by SCS. However, more research is required to establish the superiority of HOPE in increasing transplant survival.