Dataset Information

A Comprehensive Landscape of De Novo Malignancy After Double Lung Transplantation.

ABSTRACT: Although the association between post-transplant malignancy (PTM) and immunosuppressive therapy after organ transplantation has been studied, an integrated review of PTM after lung transplantation is lacking. We investigated the incidence and types of de novo PTM and its impact on survival following double lung transplantation (DLT). The incidence and type of PTM as well as the annual and cumulative risks of each malignancy after DLT were analyzed. The overall survival (OS) of recipients with or without PTM was compared by the Kaplan-Meier survival method and landmark analysis. There were 5,629 cases (23.52%) with 27 types of PTMs and incidences and OS varied according to the types of PTMs. The recipients with PTM showed a significantly longer OS than those without PTM (p < 0.001). However, while the recipients with PTM showed significantly better OS at 3, and 5 years (p < 0.001, p = 0.007), it was worse at the 10-year landmark time (p = 0.013). And the single PTM group showed a worse OS rate than the multiple PTM group (p < 0.001). This comprehensive report on PTM following DLT can help understand the risks and timing of PTM to improve the implementation of screening and treatment.

SUBMITTER: Lee J

PROVIDER: S-EPMC10468575 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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A Comprehensive Landscape of <i>De Novo</i> Malignancy After Double Lung Transplantation.

Lee Jeeyeon J Yang Andrew Won Jun AWJ Chung Liam Il-Young LI Yu Jisang J Lee Yunjoo Y Kim Hye Sung HS Shin Hyun Joon HJ Choi Young-Geun YG Bharat Ankit A Chae Young Kwang YK

Transplant international : official journal of the European Society for Organ Transplantation 20230817

Although the association between post-transplant malignancy (PTM) and immunosuppressive therapy after organ transplantation has been studied, an integrated review of PTM after lung transplantation is lacking. We investigated the incidence and types of <i>de novo</i> PTM and its impact on survival following double lung transplantation (DLT). The incidence and type of PTM as well as the annual and cumulative risks of each malignancy after DLT were analyzed. The overall survival (OS) of recipients ...[more]

PMID: 37663524

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Project description:BackgroundLong-read sequencing (LRS) techniques have been very successful in identifying structural variants (SVs). However, the high error rate of LRS made the detection of small variants (substitutions and short indels < 20 bp) more challenging. The introduction of PacBio HiFi sequencing makes LRS also suited for detecting small variation. Here we evaluate the ability of HiFi reads to detect de novo mutations (DNMs) of all types, which are technically challenging variant types and a major cause of sporadic, severe, early-onset disease.MethodsWe sequenced the genomes of eight parent-child trios using high coverage PacBio HiFi LRS (~ 30-fold coverage) and Illumina short-read sequencing (SRS) (~ 50-fold coverage). De novo substitutions, small indels, short tandem repeats (STRs) and SVs were called in both datasets and compared to each other to assess the accuracy of HiFi LRS. In addition, we determined the parent-of-origin of the small DNMs using phasing.ResultsWe identified a total of 672 and 859 de novo substitutions/indels, 28 and 126 de novo STRs, and 24 and 1 de novo SVs in LRS and SRS respectively. For the small variants, there was a 92 and 85% concordance between the platforms. For the STRs and SVs, the concordance was 3.6 and 0.8%, and 4 and 100% respectively. We successfully validated 27/54 LRS-unique small variants, of which 11 (41%) were confirmed as true de novo events. For the SRS-unique small variants, we validated 42/133 DNMs and 8 (19%) were confirmed as true de novo event. Validation of 18 LRS-unique de novo STR calls confirmed none of the repeat expansions as true DNM. Confirmation of the 23 LRS-unique SVs was possible for 19 candidate SVs of which 10 (52.6%) were true de novo events. Furthermore, we were able to assign 96% of DNMs to their parental allele with LRS data, as opposed to just 20% with SRS data.ConclusionsHiFi LRS can now produce the most comprehensive variant dataset obtainable by a single technology in a single laboratory, allowing accurate calling of substitutions, indels, STRs and SVs. The accuracy even allows sensitive calling of DNMs on all variant levels, and also allows for phasing, which helps to distinguish true positive from false positive DNMs.

Dataset Information

A Comprehensive Landscape of De Novo Malignancy After Double Lung Transplantation.

Publications

A Comprehensive Landscape of <i>De Novo</i> Malignancy After Double Lung Transplantation.

Similar Datasets

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