Abstract 7338: Prevalence and risk factors of PALB2 germline pathogenic variants
Authors: Kang Min-Chae , Jung Ye-Ryeong , Lee Seeyoun , Kang Han-Sung , Jung So-Youn , Lim Myong Cheol , Lee Keun Seok , Lee Eun-Gyeong , Kong Sun-Young 
Published: March 2024

Background: PALB2, located on chromosome 16, plays a vital role in DNA damage repair as a partner and localizer of BRCA2. PALB2 germline pathogenic variant has been known to increase the risks of breast cancer, pancreatic cancer, and ovarian cancer. However, the prevalence of PALB2 germline variants in Korean patients has not been thoroughly investigated. This study aimed to evaluate the prevalence of PALB2 germline variants and the risk factors in Korean population. Methods: We analyzed the data of 3755 patients who performed hereditary cancer germline next generation sequencing (NGS) panels, including PALB2, at the National Cancer Center in Korea between 2008 and 2022. Genetic variants were classified using a five-tier system following the American College of Medical Genetics and Genomics guidelines as follows: pathogenic (PV), likely pathogenic (LPV), variants of uncertain significance (VUS), likely benign, and benign. We retrospectively reviewed 102 individuals who were confirmed to have the PALB2 germline variant with PV, LPV and VUS. Also, we analyzed the clinical characteristics of patients with PALB2 heterozygous PV or LPV.

Results: A total of 102 patients (2.7%, 102/3755) represented PALB2 germline variants with 81 (79.4%) VUS, 14 (13.7%) LPV, and 7 (6.9%) PV. Detected twelve germline PALB2 LPV or PV were as followings; c.3350+5G&gt;A (n=6), c.454A&gt;T (n=3), c.1048C&gt;T (n=2), c.2016dup (n=2), c.1424C&gt;G (n=1), c.1976_1977del (n=1), c.2095dup (n=1), c.2834+2T&gt;C (n=1), c.2920_2921delAA (n=1), c.3317delT (n=1), c.902delA (n=1), and exon 11 deletion (n=1). 35 PALB2 VUS were detected in 81 patients. Among 21 female patients with LPV or PV (median diagnosis age 50 years; 25-69), 18 carriers (85.7%) and 3 carriers (14.3%) were diagnosed with breast cancer and ovarian cancer, respectively. For 18 breast cancer patients, 3 patients had bilateral breast cancer and 3 patients had multi-organ cancers (ovary, thyroid, or colorectal and gastric cancer).Also, 15 carriers (71.4%) have first-degree relatives with breast, ovarian, pancreatic, lung, gastric, liver, thyroid, and colorectal cancer and 10 carriers (47.6%) have second-degree relatives with breast, pancreatic, lung, gastric, liver, prostate, lymphoma, laryngeal, and uterine cancer.

Conclusion: In our study, PALB2 germline PV or LPV were detected at a low frequency of 0.56% in Korean cancer patients. Family history was an important risk factor for suspected germline pathogenic variants, and bilateral breast cancer was observed in 16.7% of breast cancer patients who harbored PALB2 PV or LPV. This study was supported by grant from the National Cancer Center. (grant number HA23C0419; NCC- 23F1850; NCC-2110181).

Citation Format: Min-Chae Kang, Ye-Ryeong Jung, Seeyoun Lee, Han-Sung Kang, So-Youn Jung, Myong Cheol Lim, Keun Seok Lee, Eun-Gyeong Lee, Sun-Young Kong. Prevalence and risk factors of PALB2 germline pathogenic variants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7338.