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Genomics-based personalized oncology in cancer of unknown primary (CUP, project H021)

To perform a comprehensive genomic characterization of 70 patients suffering from cancer of unknown primary (CUP) we used whole-exome, whole-genome, transcriptome and methylome analysis. We detected a substantial mutational heterogeneity with genes most commonly affected by SNVs, indels and fusions being TP53, TTN, MUC16, ABCA13, COL6A3, KRAS, LRP1B, XIRP2 and CSMD3. The most common fusion involved FGFR2, the most common focal deletion affected CDKN2A. A molecular tumor board recommended genomics-based therapies in 56/70 (80%) patients which were applied in 20/56 (35.7%) cases. Entity predictions based on transcriptome and methylome data could be made in up to 62/70 (88.6%) cases but were conclusive in only 16/48 (33.3%) cases. Germline analysis revealed 6 (likely) pathogenic mutations in 5 patients. Recommended therapies translated into a mean PFS2/1 ratio of 3.61 (median=2.25) with a median PFS1 of 89 days (n=17) compared to a median PFS2 of 182.5 days (n=20). Our data emphasize the clinical benefit of comprehensive genetic approaches in diagnostic and therapeutic management and underline the need for innovative, mechanism-based clinical trials in this heterogeneous group of diseases.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001006613 Illumina HiSeq 2000 Illumina HiSeq 2500 Illumina HiSeq 4000 -
EGAD00001006614 HiSeq X Ten -
EGAD00001006615 HiSeq X Ten Illumina HiSeq 2000 Illumina HiSeq 2500 Illumina HiSeq 4000 -
EGAD00001008638 -
EGAD00001008669 1
EGAD00010002036 Illumina 850k 55
Publications Citations
Comprehensive genomic and epigenomic analysis in cancer of unknown primary guides molecularly-informed therapies despite heterogeneity.
Nat Commun 13: 2022 4485
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