Malignant transformation and genetic alterations are uncoupled in early colorectal cancer progression

Soulafa Mamlouk, Tincy Simon, Laura Tomás, David C. Wedge, Alexander Arnold, Andrea Menne, David Horst, David Capper, Markus Morkel, David Posada, Christine Sers, Hendrik Bläker

Research output: Contribution to journalArticlepeer-review


Colorectal cancer (CRC) development is generally accepted as a sequential process, with genetic mutations determining phenotypic tumor progression. However, matching genetic profiles with histological transition requires the analyses of temporal samples from the same patient at key stages of progression.

Here, we compared the genetic profiles of 34 early carcinomas with their respective adenomatous precursors to assess timing and heterogeneity of driver alterations accompanying the switch from benign adenoma to malignant carcinoma. In almost half of the cases, driver mutations specific to the carcinoma stage were not observed. In samples where carcinoma-specific alterations were present, TP53 mutations and chromosome 20 copy gains commonly accompanied the switch from adenomatous tissue to carcinoma. Remarkably, 40% and 50% of high-grade adenomas shared TP53 mutations and chromosome 20 gains, respectively, with their matched carcinomas. In addition, multi-regional analyses revealed greater heterogeneity of driver mutations in adenomas compared to their matched carcinomas.

Genetic alterations in TP53 and chromosome 20 occur at the earliest histological stage in colorectal carcinomas (pTis and pT1). However, high-grade adenomas can share these alterations despite their histological distinction. Based on the well-defined sequence of CRC development, we suggest that the timing of genetic changes during neoplastic progression is frequently uncoupled from histological progression.
Original languageEnglish
JournalBMC Biology
Issue number1
Early online date7 Sept 2020
Publication statusE-pub ahead of print - 7 Sept 2020


Dive into the research topics of 'Malignant transformation and genetic alterations are uncoupled in early colorectal cancer progression'. Together they form a unique fingerprint.

Cite this