{"id":13027,"date":"2026-03-19T16:00:20","date_gmt":"2026-03-19T16:00:20","guid":{"rendered":"http:\/\/sebigec.es\/blog\/?guid=63edfb90cc22a33c355dd61f3d5db059"},"modified":"2026-03-19T16:00:20","modified_gmt":"2026-03-19T16:00:20","slug":"comparison-of-clinical-characteristics-between-patients-with-single-mutation-and-co-mutation-in-hereditary-renal-cancer-a-retrospective-analysis-of-115-patients-with-von-hippel-lindau-syndrome","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2026\/03\/19\/comparison-of-clinical-characteristics-between-patients-with-single-mutation-and-co-mutation-in-hereditary-renal-cancer-a-retrospective-analysis-of-115-patients-with-von-hippel-lindau-syndrome\/","title":{"rendered":"Comparison of clinical characteristics between patients with single mutation and co-mutation in hereditary renal cancer: a retrospective analysis of 115 patients with von Hippel-Lindau syndrome"},"content":{"rendered":"<sec><st>Purpose<\/st><p>von Hippel-Lindau (VHL) syndrome-related renal cell carcinoma (RCC) is the most prevalent hereditary RCC and exhibits clinical heterogeneity, complicating patient management. While <I>VHL<\/I> gene inactivation is the primary driver, the impact of co-occurring germline mutations in other renal cancer predisposition genes on clinical phenotype remains poorly understood. This study aimed to investigate whether such co-mutations define a distinct clinical and molecular subgroup of patients with VHL syndrome.<\/p><\/sec><sec><st>Methods<\/st><p>115 patients with VHL syndrome were enrolled in this study. All patients underwent germline sequencing of a 39-gene panel for hereditary RCC. Pathogenic\/likely pathogenic variants of the <I>VHL<\/I> gene were identified, and patients were stratified into a VHL single-mutation group and a VHL co-mutation group. Clinical characteristics, tumour manifestations, renal lesion growth kinetics and age-related tumour risks were compared.<\/p><\/sec><sec><st>Results<\/st><p>42.6% of patients harboured germline co-mutations. The co-mutation group exhibited a greater proportion of symptomatic patients (95.9% vs 78.7%, p=0.012) and increased penetrance of RCC (79.6% vs 57.6%, p=0.013) and pancreatic cystic tumours (77.6% vs 48.5%, p=0.002). This group had a lower incidence of positive family history (40.8% vs 69.7%, p=0.002). Co-mutation status is an independent predictor for RCC development (HR 1.798, p=0.016), and their RCC lesions exhibited significantly faster linear (0.376 cm\/year vs 0.225 cm\/year, p=0.022) and volumetric (3.132 cm<sup>3<\/sup>\/year vs 1.167 cm<sup>3<\/sup>\/year, p=0.049) growth metrics.<\/p><\/sec><sec><st>Conclusions<\/st><p>Germline co-mutations are prevalent in VHL syndrome and define a clinically distinct subset of patients characterised by higher disease penetrance and a more aggressive RCC phenotype. Our findings suggest that co-mutation status is a critical determinant of clinical heterogeneity and a powerful biomarker for risk stratification.<\/p><\/sec>","protected":false},"excerpt":{"rendered":"<p>Purposevon Hippel-Lindau (VHL) syndrome-related renal cell carcinoma (RCC) is the most prevalent hereditary RCC and exhibits clinical heterogeneity, complicating patient management. While VHL gene inactivation is the primary driver, the impact of co-oc&#8230;<\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,8,9],"tags":[],"class_list":["post-13027","post","type-post","status-publish","format-standard","hentry","category-articulos","category-jmg-first","category-open-access"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/13027","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=13027"}],"version-history":[{"count":1,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/13027\/revisions"}],"predecessor-version":[{"id":13028,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/13027\/revisions\/13028"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=13027"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=13027"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=13027"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}