Oncotator: Cancer variant annotation tool. genes. It is characterized by a CCI-006 marked increase in the lifetime risk of CRC and extra\colorectal cancers (Hampel et?al.,?2008). For clinical diagnosis of LS, diagnostic algorithms that take into account medical history, including Amsterdam I/II criteria (AC) (Vasen, Watson, Mecklin, & Lynch,?1999) and revised Bethesda guidelines (BG) (Umar et?al.,?2004), have been developed. The advances made in next\generation sequencing (NGS) technology over the last decade have made it possible to identify suspected LS patients and affected families on the basis of clinical history and the molecular tumor phenotype. Multigene cancer panel testing of suspected LS patients along with diagnosis based on AC and BG criteria has allowed the identification of an increasing number of variants other than variants. variants represent a large fraction of these new variants. is involved in homologous recombination (HR), which is an error\free repair mechanism for DNA double\strand breaks (Moynahan, Pierce, & Jasin,?2001). Defective can cause hereditary breast and ovarian cancers (Llort et?al.,?2015; Mavaddat et?al.,?2013). Breast cancer cells with variants in (OMIM accession number: 113705), or (OMIM accession number: 600185) develop extreme sensitivity to poly ADP\ribose polymerase (PARP) inhibitors and cytotoxic drugs (Abbotts et?al.,?2019). In addition to variants, variants of CCI-006 other genes involved in HR have been detected by multigene panel testing (Brand?o et?al.,?2019; Feliubadal et?al.,?2019). Abberation of other proteins in HR repair pathways, such as (OMIM accession number: 179617), (OMIM accession number: 607585), and (OMIM accession number: 601215), also results in impaired HR (Abbotts et?al.,?2019; Venkitaraman,?2003). Tumors bearing these abnormalities, described as variants have been identified based on NGS data of suspected LS patients, and some studies have revealed a CCI-006 higher incidence of CRC in subjects carrying variants (Kwong et?al.,?2016; Mersch et?al.,?2015; Phelan et?al.,?2014; Lin et al., 1999; Moran et?al.,?2012; Van Asperen et?al.,?2005; Brose et?al.,?2002; Chalasani,?1999; Suchy et?al.,?2010; Kirchhoff et?al.,?2004; Niell et?al.,?2004; Risch et?al.,?2001; Struewing et?al.,?1997; Yurgelun et?al.,?2015; Yurgelun et?al.,?2017). However, studies on phenotypic characteristics, variants, and the pedigrees of and and and CRC. To the best of our knowledge, this is the first study to describe variants in suspected LS patients. Further, we newly introduce the concept of an association between variants, and 11 carrying variants of unknown significance (VUS) or variants of other genes, were excluded. Patients carrying PVs in were classified as the group, whereas patients carrying and test, respectively, in SPSS v. 21.0 software (SPSS). OS and PFS were evaluated using KaplanCMeier curves and were compared using the log\rank test. A two\tailed group (44.95??10.86?years; group (69.0% (29/42); group (valuevaluestage0.447.800N030 (71.4%)13 (65.0%)N18 (19.0%)4 (20.0%)N24 (9.6%)3 (15.0%)Metastasis0.616.433Occurrence2 (4.8%)2 (10.0%)Absence40 (95.2%)18 (90.0%)TNM stage0.684.877I12 (28.6%)6 (30.0%)II16 (38.1%)7 (35.0%)III12 (28.6%)5 (25.0%)IV2 (4.8)2 (10.0%) Open in a separate window aThese data are presented as mean??standard deviation; other values are presented as number of patients followed by percentage in parentheses. A comparison of tumor histories revealed significant differences between the two groups in the total number of cancers, the earliest cancer\onset age, occurrence CCI-006 of metachronous CRCs, and the number of CRCs. The total number of cancers was 1.30 (0.57) in the group CCI-006 (group. The characteristics of tumor histories of the 62 patients in the two groups were compared and are summarized in Table?2. TABLE 2 Characteristic of tumor histories in patients (group (valuevaluegroup (group, but in only 1 1 (14.3%, 1/7) patient in the group (group and in one (7.7%, 1/13) patient of the group and two (10.0%) patients in the group and 102.3 (58.7) months in the group, and 100.0%, 87.5%, and 72.9%, respectively, in the group and group after surgery As for PFS, 23 probands experienced CTCF tumor progression, including 14 patients with metachronous CRC, 8 with metastasis, and 7 with extra\colorectal tumors in the group. In the group (group, and 95.7%, 77.2%, and 77.2%, respectively, in the group and group after surgery For early\onset CRC patients, 1\, 3\, and.