Lorcaserin-induced rat mammary mutants quantified by CarcSeq

Lorcaserin, a drug for weight management, is a selective agonist of the serotonin (5-hydroxytryptamine) 2C receptor. Although lorcaserin is a non-genotoxic rat carcinogen, FDA approval was granted in part based on dose extrapolation considerations. A post-marketing study, CAMELLIA-TIMI, designed to detect potential cardiovascular effects of lorcaserin therapy detected excess cancer risk in the lorcaserin treatment arm. Consequently, a study of lorcaserin-treated rats was conducted to elucidate the mechanism of lorcaserin-induced carcinogenesis and facilitate detection of other carcinogens operating through the same mechanism in the future. Another study goal was to characterize CarcSeq utility in detecting the neoplasia-related effects of a non-genotoxic carcinogen. CarcSeq is an error-corrected next-generation sequencing method for quantitation of panels of hotspot cancer driver mutations (CDMs) and can detect mutations with mutant fractions (MFs) ≥10-4. Female Sprague Dawley rats were..., Study Rationale
There is a need to improve the assessment of carcinogenic risk associated with exposure to various test articles, including pharmaceuticals intended for chronic use. The need is particularly acute in terms of detecting the carcinogenic impacts of non-genotoxic carcinogens. The CarcSeq error corrected sequencing method was developed as an approach to address this need. CarcSeq was designed to quantify mutant fraction (MF, mutant bases per total number of bases characterized at a given position) of mutants in segments of DNA encompassing hotspot cancer driver mutations (CDMs), including segments of the Apc, Braf, Hras, Kras, Nfe2l2, Pik3ca, Setbp1, Stk11, and Tp53 genes. Using CarcSeq, it was shown that CDMs with MFs greater than or equal to 10<sup>-4</sup> are present in normal human tissues [1], as well as untreated tissues (mammary and lung) of rat and mouse [2,3]. Given that spontaneously occurring CDMs are obligatory for carcinogenesis induced by a no..., , # Data from: Lorcaserin-induced rat mammary mutants quantified by CarcSeq

## Description of the data and file structure

Although three datasets were generated in the conduct of this study, based upon dataset size considerations, only one dataset is provided to enable independent re-analysis of CarcSeq output. Specifically, the data obtained in the replications of the CarcSeq analysis of the 24-week samples is provided (24 week replicate 2, Rep 2). The data is provided in the form of one compressed folder for the sequencing output of each rat treated for 24 weeks. More precisely, each compressed folder contains all the fastq files produced by the CarcSeq analysis of genomic DNA from one rat that were run through the Kennedy error correction pipeline [8] and post-error correction filtering steps to obtain the final data. The folder naming convention uses M to signify mammary tissue as the source of genomic DNA, incorporates the rat identifier number (ID#, between 19 and 36 for the rats ...,