Kallmann Syndrome and MSI-H Colorectal Cancer in a Patient with a Germline PROKR2 Variant: A Case Report with Exploratory Cohort Analysis
5 affiliations
- 1Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
- 2Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou 310022, China
- 3Department of Endocrinology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
- 4Cancer Center, Zhejiang University, Hangzhou 310058, China
- 5Center for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, Hangzhou 310009, China
Abstract
PROKR2 is an established gene associated with Kallmann syndrome (KS), and preclinical studies have suggested a possible role in tumor development. In this study, we report a patient with KS and microsatellite instability-high (MSI-H) colon cancer and aim to explore the potential association between PROKR2 variants and MSI-H status in colorectal cancer (CRC). Peripheral blood samples from the proband and his parents underwent whole-exome sequencing (WES) to identify germline variants. The WES revealed that both the proband and his father carried a likely pathogenic variant in the KS-associated gene PROKR2 (NM_144773.4:c.337T>C, p.Tyr113His). To place this case in a broader context, we performed exploratory bioinformatic analyses of somatic PROKR2 variants in two public CRC cohorts, DFCI-CRC and TCGA-CRC, although these cohort analyses cannot inform germline risk. In the DFCI-CRC cohort, PROKR2 somatic variant status showed no statistically significant association with MSI-H status in either the unadjusted or TMB-adjusted analysis. In the TCGA-CRC cohort, PROKR2 somatic variants were associated with higher unadjusted odds of MSI-H (OR = 5.50, 95% CI = 1.003–30.20, p = 0.0248, BH-adjusted q = 0.0495). After TMB adjustment, this positive association was not retained and the adjusted estimate was in the opposite direction (adjusted OR = 0.093, 95% CI = 0.014–0.549, p = 0.00875, BH-adjusted q = 0.0175). Accordingly, this case report describes the co-occurrence of PROKR2-related KS and MSI-H CRC in a single patient, although a causal relationship between PROKR2-related KS and CRC remains unestablished.
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BibTeX
@article{lu2026kallmann,
title = {{Kallmann Syndrome and MSI-H Colorectal Cancer in a Patient with a Germline PROKR2 Variant: A Case Report with Exploratory Cohort Analysis}},
author = {Yier Lu and Dan Li and Weiwei Liang and Ziyan Tong and Xiuyuan Zhang and Yan He and Ningjuan Yu and Shanshan Weng and Ying Yuan and Mengyuan Yang},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219703},
url = {https://www.mdpi.com/1422-0067/27/21/9703},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Kallmann Syndrome and MSI-H Colorectal Cancer in a Patient with a Germline PROKR2 Variant: A Case Report with Exploratory Cohort Analysis
AU - Yier Lu
AU - Dan Li
AU - Weiwei Liang
AU - Ziyan Tong
AU - Xiuyuan Zhang
AU - Yan He
AU - Ningjuan Yu
AU - Shanshan Weng
AU - Ying Yuan
AU - Mengyuan Yang
PY - 2026
DA - 2026/10/29
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219703
UR - https://www.mdpi.com/1422-0067/27/21/9703
AB - PROKR2 is an established gene associated with Kallmann syndrome (KS), and preclinical studies have suggested a possible role in tumor development. In this study, we report a patient with KS and microsatellite instability-high (MSI-H) colon cancer and aim to explore the potential association between PROKR2 variants and MSI-H status in colorectal cancer (CRC). Peripheral blood samples from the proband and his parents underwent whole-exome sequencing (WES) to identify germline variants. The WES revealed that both the proband and his father carried a likely pathogenic variant in the KS-associated gene PROKR2 (NM_144773.4:c.337T>C, p.Tyr113His). To place this case in a broader context, we performed exploratory bioinformatic analyses of somatic PROKR2 variants in two public CRC cohorts, DFCI-CRC and TCGA-CRC, although these cohort analyses cannot inform germline risk. In the DFCI-CRC cohort, PROKR2 somatic variant status showed no statistically significant association with MSI-H status in either the unadjusted or TMB-adjusted analysis. In the TCGA-CRC cohort, PROKR2 somatic variants were associated with higher unadjusted odds of MSI-H (OR = 5.50, 95% CI = 1.003–30.20, p = 0.0248, BH-adjusted q = 0.0495). After TMB adjustment, this positive association was not retained and the adjusted estimate was in the opposite direction (adjusted OR = 0.093, 95% CI = 0.014–0.549, p = 0.00875, BH-adjusted q = 0.0175). Accordingly, this case report describes the co-occurrence of PROKR2-related KS and MSI-H CRC in a single patient, although a causal relationship between PROKR2-related KS and CRC remains unestablished.
SN - 1422-0067
ER -