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Familial colorectal cancer type X (FCCTX) is characterized by clinical features of hereditary non-polyposis colorectal cancer with a yet undefined genetic background. Here we identify the SEMA4A p.Val78Met germline mutation in an Austrian kindred with FCCTX, using an integrative genomics strategy. Compared with wild-type protein, SEMA4A V78M demonstrates significantly increased MAPK/Erk and PI3K/Akt signalling as well as cell cycle progression of SEMA4A-deficient HCT-116 colorectal cancer cells. In a cohort of 53 patients with FCCTX, we depict two further SEMA4A mutations, p.Gly484Ala and p.Ser326Phe and the single-nucleotide polymorphism (SNP) p.Pro682Ser. This SNP is highly associated with the FCCTX phenotype exhibiting increased risk for colorectal cancer (OR 6.79, 95% CI 2.63 to 17.52). Our study shows previously unidentified germline variants in SEMA4A predisposing to FCCTX, which has implications for surveillance strategies of patients and their families. It is known that hereditary factors contribute to familial colorectal cancer type X. Here, the authors uncover the SEMA4A p.Val78Met germline mutation and show that the protein product is associated with changes in cell cycle progression in colorectal cancer cells.

Multiple myeloma (MM) is a malignant clonal expansion of plasma cells in the bone marrow and belongs to the mature B-cell neoplams. The pathogenesis of MM is associated with constitutive NF-κB activation. However, genetic alterations causing constitutive NF-κB activation are still incompletely understood. Since A20 (TNFAIP3) is a suppressor of the NF-κB pathway and is frequently inactivated in various lymphoid malignancies, we investigated the genetic and epigenetic properties of A20 in MM. In total, of 46 patient specimens analyzed, 3 single base pair exchanges, 2 synonymous mutations and one missense mutation were detected by direct sequencing. Gene copy number analysis revealed a reduced A20 gene copy number in 8 of 45 (17.7%) patients. Furthermore, immunohistochemical staining confirmed that A20 expression correlates with the reduction of A20 gene copy number. These data suggest that A20 contributes to tumor formation in a significant fraction of myeloma patients.

Multiple myeloma (MM) is a malignant clonal expansion of plasma cells in the bone marrow and belongs to the mature B-cell neoplams. The pathogenesis of MM is associated with constitutive NF- Kappa B activation. However, genetic alterations causing constitutive NF- Kappa B activation are still incompletely understood. Since A20 (TNFAIP3) is a suppressor of the NF- Kappa B pathway and is frequently inactivated in various lymphoid malignancies, we investigated the genetic and epigenetic properties of A20 in MM. In total, of 46 patient specimens analyzed, 3 single base pair exchanges, 2 synonymous mutations and one missense mutation were detected by direct sequencing. Gene copy number analysis revealed a reduced A20 gene copy number in 8 of 45 (17.7%) patients. Furthermore, immunohistochemical staining confirmed that A20 expression correlates with the reduction of A20 gene copy number. These data suggest that A20 contributes to tumor formation in a significant fraction of myeloma patients.

Objectives: Renal diseases and their treatment can cause distress and psychosocial problems for both patients and relatives. Methods: Relationship dynamics and parameters of quality of life were assessed in 10 genetically related (brothers) and 14 genetically unrelated donor-recipient pairs (spouses) involved in living kidney donation (LKD). Results: LKDs were described by related donors and recipients as fundamentally positive and in many cases led to an intensification of the relationship between donor and recipient. LKDs between unrelated donors and recipients appeared to achieve the same results as donations between related donors and recipients. Particularly the general desire to help determined the decision-making process of donors. Conclusion: In addition to general clinical parameters, especially motivational and relationship dynamics should be evaluated in the pre- and postoperative clinical psychological assessment of potential donors and recipients of LKD. Fragestellung: Nierenerkrankungen und deren Behandlung verursachen sowohl für die Patienten als auch für die Angehörigen Belastungen und psychosoziale Probleme. Methode: Für zehn genetisch verwandte (Brüderpaare) und 14 genetisch nicht-verwandte SpenderInnen-Empfänger-Paare (lebenspartnerschaftliche Paare) von Nierenlebendspenden wurden beziehungsdynamische Aspekte sowie Lebensqualitätsparameter erhoben. Ergebnisse: Die Nierenlebendspende wurde von genetisch verwandten Spender-Empfänger-Paaren als sehr positiv beschrieben und führte mehrheitlich zu einer Intensivierung der Beziehung zwischen Spender und Empfänger. Nierenlebendspenden zwischen genetisch nichtverwandten Spenderinnen-Empfänger-Paaren erreichten hierbei vergleichbare Ergebnisse. Vor allem der allgemeine Wunsch zu helfen bestimmte den Entscheidungsprozess der Spender. Diskussion: Im Rahmen des prä- und postoperativen klinisch-psychologischen Assessments von Nierenlebendspendern und -empfängern sollen neben allgemeinen klinischen Parametern vor allem motivationale und beziehungsdynamische Aspekte erhoben werden.

Renal diseases and their treatment can cause distress and psychosocial problems for both patients and relatives. Relationship dynamics and parameters of quality of life were assessed in 10 genetically related (brothers) and 14 genetically unrelated donor-recipient pairs (spouses) involved in living kidney donation (LKD). LKDs were described by related donors and recipients as fundamentally positive and in many cases led to an intensification of the relationship between donor and recipient. LKDs between unrelated donors and recipients appeared to achieve the same results as donations between related donors and recipients. Particularly the general desire to help determined the decision-making process of donors. In addition to general clinical parameters, especially motivational and relationship dynamics should be evaluated in the pre- and postoperative clinical psychological assessment of potential donors and recipients of LKD.

Zusammenfassung Fragestellung: Nierenerkrankungen und deren Behandlung verursachen sowohl für die Patienten als auch für die Angehörigen Belastungen und psychosoziale Probleme. Methode: Für zehn genetisch verwandte (Brüderpaare) und 14 genetisch nicht-verwandte SpenderInnen-Empfänger-Paare (lebenspartnerschaftliche Paare) von Nierenlebendspenden wurden beziehungsdynamische Aspekte sowie Lebensqualitätsparameter erhoben. Ergebnisse: Die Nierenlebendspende wurde von genetisch verwandten Spender-Empfänger-Paaren als sehr positiv beschrieben und führte mehrheitlich zu einer Intensivierung der Beziehung zwischen Spender und Empfänger. Nierenlebendspenden zwischen genetisch nichtverwandten Spenderinnen-Empfänger-Paaren erreichten hierbei vergleichbare Ergebnisse. Vor allem der allgemeineWunsch zu helfen bestimmte den Entscheidungsprozess der Spender. Diskussion: Im Rahmen des prä- und postoperativen klinisch-psychologischen Assessments von Nierenlebendspendern und -empfängern sollen neben allgemeinen klinischen Parametern vor allem motivationale und beziehungsdynamische Aspekte erhoben werden. Abstract The influence of relationship dynamics on the psychosocial outcome of genetically related and unrelated living kidney donor-recipient pairs Objectives: Renal diseases and their treatment can cause distress and psychosocial problems for both patients and relatives. Methods: Relationship dynamics and parameters of quality of life were assessed in 10 genetically related (brothers) and 14 genetically unrelated donor-recipient pairs (spouses) involved in living kidney donation (LKD). Results: LKDs were described by related donors and recipients as fundamentally positive and in many cases led to an intensification of the relationship between donor and recipient. LKDs between unrelated donors and recipients appeared to achieve the same results as donations between related donors and recipients. Particularly the general desire to help determined the decision-making process of donors. Conclusion: In addition to general clinical parameters, especially motivational and relationship dynamics should be evaluated in the pre- and postoperative clinical psychological assessment of potential donors and recipients of LKD.