ESMO Open shared an article led by M.-C. Kang on X about the frequency, clinical features, and functional implications of the PALB2 germline pathogenic variant c.3350+5G>A in a cohort of 3987 Korean cancer patients.

PALB2 germline pathogenic variants: frequency, clinical features, and functional analysis of c.3350+5G>A variant in 3987 Korean cancer patients

Authors: M.-C. Kang, S. Lee, H. Kim, H.-S. Kang, S.-Y. Jung, J.-A. Hwang, J. Kwon, K.S. Lee, M.C. Lim, S.-Y. Park, S.H. Sim, W. Choi, J.E. Park, E.-H. Cho, S.-Y. Kong

Frequency, Clinical Features, and Functional Analysis of the PALB2 c.3350+5G>A Germline Pathogenic Variant

This study aimed to evaluate the prevalence and clinical characteristics of PALB2 germline variants in a cohort of 3987 Korean cancer patients.

The analysis revealed that 0.6% of patients had pathogenic or likely pathogenic variants (PV/LPV) in PALB2, with 95.5% of these patients being women. The majority of those with PV/LPV were diagnosed with breast or ovarian cancer. Additionally, the study reclassified the c.3350+5G>A variant as pathogenic, according to the American College of Medical Genetics and Genomics guidelines, which had previously been considered a variant of uncertain significance.

The study also found that patients with PALB2 PV/LPVs had a younger age at first cancer diagnosis (44.6 years on average) compared to those without these variants (50.2 years). Furthermore, these patients were more likely to have multiple primary cancers, with 22.7% of them having more than one cancer compared to only 8.3% in those without PV/LPV.

These findings suggest that age at diagnosis and the presence of multiple primary cancers may serve as key risk factors for identifying patients with germline PALB2 variants. The authors emphasize the need for improved adherence to the National Comprehensive Cancer Network guidelines for cancer screening and family genetic testing among Korean cancer patients.