bims-lifras 2024-07-07 papers

Issue of 2024–07–07
three papers selected by
Joanna Zawacka, Karolinska Institutet

Lung Cancer. 2024 Jun 28. pii: S0169-5002(24)00398-2. [Epub ahead of print]194 107864

Prevalence of pathogenic or likely pathogenic germline variants in cancer predisposition genes among selected patients with lung adenocarcinoma: The GERMLUNG study.

Oscar Arrieta, Enrique Caballé-Pérez, Norma Hernández-Pedro, Eunice Romero-Nuñez, José Lucio-Lozada, Cesar Castillo-Ruiz, Karla Acevedo-Castillo, Rosa María Álvarez-Gómez, Carolina Molina-Garay, Marco Jiménez-Olivares, Karol Carrillo-Sánchez, Elvia Cristina Mendoza-Caamal, Andrés F Cardona, Jordi Remon, Carmen Alaez-Verson.

INTRODUCTION: Pathogenic or likely pathogenic germline variants (PGVs) in cancer predisposition genes may play a role in lung cancer (LC) susceptibility. However, determining an eligible population for genetic testing remains uncertain. This study aimed to assess the prevalence of PGVs in a selected cohort of individuals with lung adenocarcinoma.
METHODS: A cross-sectional cohort study was conducted to assess the PGVs rate in lung adenocarcinoma patients with a family history of LC, young-onset presentation, history of never/light smoking, or actionable genomic alterations (AGAs). Sequencing was performed using Sophia Hereditary Cancer Solution panel F, including 144 cancer predisposition genes. Variants classified as pathogenic or likely pathogenic were included for further analysis.
RESULTS: Of 201 patients, 43 (21.4 %) exhibited PGVs, among which 64.5 % were DNA damage repair genes, and 86.1 % were clinically actionable. The main PGVs were in ATM (9.3 %), TP53 (6.9 %), BRCA2 (6.9 %), and CHEK2 (6.9 %) genes. PGVs were associated with male sex (adjusted odds ratio [aOR] 2.46, 95 % CI 1.15-5.32, p = 0.021), along with a trend toward association with AGAs (aOR 6.04, 95 % CI 0.77-49.74, p = 0.094).
CONCLUSIONS: In this study, a high PGVs prevalence was identified based on our selection criteria, which represents an effective strategy to identify candidates for germline genomic testing, potential screening strategies in close relatives, and personalized therapeutic modalities. Our results warrant further exploration in other populations to confirm them.

Keywords: Actionable genomic alterations; Adenocarcinoma of lung; Germline Pathogenic/Likely pathogenic variants; Hereditary; Neoplastic syndromes

DOI: https://doi.org/10.1016/j.lungcan.2024.107864

Oncotarget. 2024 Jul 02. 15 442-443

DDX41 and its unique contribution to myeloid leukemogenesis.

Hirotaka Matsui.

Keywords: DDX41; R-loop; acute myeloid leukemia; myelodysplastic neoplasms; myeloid neoplasms with germline predisposition

DOI: https://doi.org/10.18632/oncotarget.28603

Cancer Genet. 2024 Jun 22. pii: S2210-7762(24)00025-5. [Epub ahead of print]286-287 25-28

A comparison of WHO-5 and ICC classifications in a series of myeloid neoplasms, considerations for hematopathologists and molecular pathologists.

Margaret E Moore, Eli Williams, Lauren Pelkey, Elizabeth L Courville.

OBJECTIVES: The International Consensus Classification (ICC) and 5th Edition of the World Health Organization Classification (WHO-5) made substantive updates to the classification of myeloid neoplasms. This study compares the systems in a series of myeloid neoplasms with increased blasts, analyzing implications for diagnostic workflow and reporting.
METHODS: Bone marrow biopsies categorized as myelodysplastic syndrome with excess blasts (MDS-EB) or acute myeloid leukemia (AML) by WHO-R4 were identified. Results of morphology review, karyotype, fluorescence in situ hybridization, and next-generation sequencing were compiled. Cases were retrospectively re-classified by WHO-5 and ICC.
RESULTS: 46 cases were reviewed. 28 cases (61 %) had ≥20 % blasts, with the remaining cases having 5-19.5 % blasts. The most common differences in classification were 1) the designation of MDS versus MDS/AML (10/46, 22 %) for cases with 10-19 % blasts and 2) the ICC's designation of TP53 variants as a separate classifier for AML (8/46, 17 %). Bi-allelic/multi-hit TP53 alterations were identified in 15 cases (33 %). Variants of potential germline significance were identified in 29 (63 %) cases.
CONCLUSIONS: While terminology differences between WHO-5 and ICC exist, both systems invoke similar opportunities for improved reporting: standardized classification of pathogenic variants (notably TP53), streamlined systems to evaluate for potential germline variants, and integrated reporting of morphologic and genetic data.

Keywords: Acute myeloid leukemia; Blasts; Interdisciplinary classification; Myelodysplastic syndrome/neoplasm; Myeloid neoplasia; Pathogenic variant classification; Pathology reporting

DOI: https://doi.org/10.1016/j.cancergen.2024.06.003