Publikationen unter Beteiligung des Zentrums für erbliche Tumorerkrankungen

Im Rahmen der Forschung publizieren unsere Mitarbeiter ihre Ergebnisse. Im Folgenden finden Sie eine Liste an ausgewählten Publikationen von unseren Mitarbeitern im Zentrum für erbliche Tumorerkrankungen.

 

Aktuelle Publikationen

 

Comprehensive analysis of the MLH1 promoter region in 480 patients with colorectal cancer and 1150 controls reveals new variants including one with a heritable constitutional MLH1 epimutation.

"We report the second promoter variant stably inducing a hereditary CEM. Concerning the classification of promoter variants, we discuss contradictory results from the literature for two variants, describe classification discrepancies between existing rules for five variants, suggest the (re-)classification of five promoter variants to (likely) benign and regard four variants as functionally unclear."

Morak M et al. J Med Genet. 2018 Feb 22. pii: jmedgenet-2017-104744. doi: 10.1136/jmedgenet-2017-104744.

 

Identification of genetic variants for clinical management of familial colorectal tumors.

"Among high-risk CRC patients that fulfill the AMS criteria or revised Bethesda guidelines, targeted gene sequencing identified likely pathogenic variant and VUS in other genes than the MMR genes (CHEK2, NOTCH3 and MAP3K1). Our study suggests that the analysis of genes currently excluded from routine molecular diagnostic screens may confer cancer susceptibility."

Dominguez-Valentin M et al. BMC Med Genet. 2018 Feb 20;19(1):26. doi: 10.1186/s12881-018-0533-9.

 

Genetic variants of prospectively demonstrated phenocopies in BRCA1/2 kindreds.

"We identified 48 women who were tested negative for their family's path_BRCA1 (n = 13) or path_BRCA2 (n = 35) variants. Pathogenic variants in the ATM, BRCA2, MSH6 and MUTYH genes were found in 10% (5/48) of the cases, of whom 15% (2/13) were from path_BRCA1 and 9% (3/35) from path_BRCA2 families. Out of the 26 unique VUS, 3 (12%) were predicted to affect RNA splicing (APC c.721G > A, MAP3K1 c.764A > G and MSH2 c.815C > T). However, by using a minigene, assay we here show that APC c.721G > A does not cause a splicing defect, similarly to what has been recently reported for the MAP3K1 c.764A > G. The MSH2 c.815C > T was previously described as causing partial exon skipping and it was identified in this work together with the path_BRCA2 c.9382C > T (p.R3128X).

All women in breast or breast/ovarian cancer kindreds would benefit from being offered genetic testing irrespective of which causative genetic variants have been demonstrated in their relatives."

Dominguez-Valentin M et al. Hered Cancer Clin Pract. 2018 Jan 15;16:4. doi: 10.1186/s13053-018-0086-0. eCollection 2018.

 

Role of germline aberrations affecting CTNNA1, MAP3K6 and MYD88 in gastric cancer susceptibility.

"Predicted deleterious germline variants were not encountered in MYD88, but recurrently observed in CTNNA1 (n=2) and MAP3K6 (n=3) in our cohort of patients with GC. In contrast to deleterious variants in CTNNA1, deleterious variants in MAP3K6 also occur frequently in the general population.

Based on our results MAP3K6 should no longer be considered a GC predisposition gene, whereas deleterious CTNNA1 variants are confirmed as an infrequent cause of GC susceptibility. Biallelic MYD88 germline mutations are at most a very rare cause of GC susceptibility as no additional cases were identified."

Weren RDA et al. J Med Genet. 2018 Jan 12. pii: jmedgenet-2017-104962. doi: 10.1136/jmedgenet-2017-104962.

 

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