Germline mutations in the human MSH2, MLH1, PMS2 and PMS1 DNA mismatch repair (MMR) gene homologues appear to be responsible for most cases of hereditary non-polyposis colorectal cancer (HNPCC; refs 1-5). An important role for DNA replication errors in colorectal tumorigenesis has been suggested by the finding of frequent alterations in the length of specific mononucleotide tracts within genes controlling cell growth, including TGF-beta receptor type II (ref. 6), BAX (ref. 7) and APC (ref. 8). A broader role for MMR deficiency in human tumorigenesis is implicated by microsatellite instability in a fraction of sporadic tumours, including gastric, endometrial and colorectal malignancies. To better define the role of individual MMR genes in cancer susceptibility and MMR functions, we have generated mice deficient for the murine homologues of the human genes MLH1, PMS1 and PMS2. Surprisingly, we find that these mice show different tumour susceptibilities, most notably, to intestinal adenomas and adenocarcinomas, and different mutational spectra. Our results suggest that a general increase in replication errors may not be sufficient for intestinal tumour formation and that these genes share overlapping, but not identical functions.

Focal liver lesions are commonly encountered and often demonstrate nonspecific findings at initial imaging. Although most incidentally discovered liver lesions are benign, their noninvasive diagnosis is necessary, especially if they are large or atypical. Imaging characterization of focal liver lesions and exclusion of malignancy are of prime importance, particularly in high-risk populations. Contrast agent-enhanced ultrasonography of liver lesions is both accurate and reproducible for evaluation of benign and malignant liver tumors. Use of an imaging algorithm and a controlled sonographic technique, including dedicated arterial phase cine imaging and imaging every 30 seconds in the portal venous phase and the delayed (or late) phase, is essential for accurate characterization. This algorithmic analysis of focal liver lesions focuses first on the determination of malignancy by imaging the portal venous phase and the late phase; washout in these phases correlates with a malignant tumor, and sustained enhancement in these phases is suggestive that a lesion is benign. In addition, the timing and the intensity of washout differentiate hepatocellular malignancies from nonhepatocellular malignancies. Nonhepatocellular tumors demonstrate early and strong washout, whereas hepatocellular malignancies show delayed and weak washout. Subsequent analysis of dynamic real-time enhancement patterns in the arterial phase demonstrates specific enhancement patterns of common benign and malignant focal liver lesions. Hemangiomas show classic peripheral nodular enhancement, and spoke-wheel centrifugal enhancement is suggestive of focal nodular hyperplasia. Hepatic adenomas may show centripetal filling. However, arterial phase enhancement in malignancy has less specificity. Online supplemental material is available for this article. RSNA, 2017 •.

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