PMID- 29410490 OWN - NLM STAT- MEDLINE DCOM- 20190520 LR - 20230210 IS - 1530-0285 (Electronic) IS - 0893-3952 (Linking) VI - 31 IP - 6 DP - 2018 Jun TI - MYB and MYBL1 in adenoid cystic carcinoma: diversity in the mode of genomic rearrangement and transcripts. PG - 934-946 LID - 10.1038/s41379-018-0008-8 [doi] AB - MYB-NFIB and MYBL1-NFIB have been reported in ~60% of adenoid cystic carcinoma cases, but driver alterations in the remaining ~40% of adenoid cystic carcinoma remain unclear. We examined 100 adenoid cystic carcinoma cases for MYB and MYBL1 locus rearrangements by fluorescence in situ hybridization (FISH) with originally designed probe sets using formalin-fixed paraffin-embedded materials. Approximately one-third of samples were also analyzed by fusion transcript-specific RT-PCR and capture RNA sequencing. In the 27 cases with frozen materials, MYB-NFIB and MYBL1-NFIB fusion transcripts were detected in 9 (33%) and 6 cases (22%) by RT-PCR, respectively. Meanwhile, high expression of MYB (18 cases, 67%) or MYBL1 (9 cases, 33%) was detected in all 27 cases in a mutually exclusive manner, regardless of its form (full-length, truncation, or fusion transcript). Interestingly, genomic rearrangements around the corresponding highly-expressed gene were observed in all 27 cases by FISH, suggesting a causative relationship between genomic rearrangements and gene expression. Among the 100 cases, including additional 73 cases, 97 harbored genomic rearrangements in the MYB (73 cases) or MYBL1 locus (24 cases) including 10 cases with atypical FISH patterns undetectable through ordinary split FISH approaches: breakpoints far distant from MYB (5 cases) and a small NFIB locus insertion into the MYB (3 cases) or MYBL1 locus (2 cases). In clinicopathological analyses, histological grade, primary tumor size, and lymph node metastasis were identified as prognostic factors, whereas MYB/MYBL1 rearrangements were not, but were associated with histological grade. In the present study, MYB or MYBL1 locus rearrangement was detected in nearly all adenoid cystic carcinoma cases, and therefore it would be a good diagnostic marker for adenoid cystic carcinoma. However, fusion transcript-specific RT-PCR for MYB-NFIB and MYBL1-NFIB and ordinary split FISH assays for MYB and MYBL1 were less sensitive, and thus detection methods should be judiciously designed because of the diversity of rearrangement modes in adenoid cystic carcinoma. FAU - Togashi, Yuki AU - Togashi Y AD - Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan. AD - Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan. AD - Department of JFCR Cancer Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8510, Japan. FAU - Dobashi, Akito AU - Dobashi A AD - Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan. FAU - Sakata, Seiji AU - Sakata S AD - Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan. FAU - Sato, Yukiko AU - Sato Y AUID- ORCID: 0000-0003-4277-0161 AD - Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan. FAU - Baba, Satoko AU - Baba S AD - Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan. FAU - Seto, Akira AU - Seto A AD - Department of Head and Neck Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan. FAU - Mitani, Hiroki AU - Mitani H AD - Department of Head and Neck Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan. FAU - Kawabata, Kazuyoshi AU - Kawabata K AD - Department of Head and Neck Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan. FAU - Takeuchi, Kengo AU - Takeuchi K AUID- ORCID: 0000-0002-1599-5800 AD - Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan. kentakeuchi-tky@umin.net. AD - Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan. kentakeuchi-tky@umin.net. AD - Department of JFCR Cancer Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8510, Japan. kentakeuchi-tky@umin.net. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180206 PL - United States TA - Mod Pathol JT - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JID - 8806605 RN - 0 (MYB protein, human) RN - 0 (MYBL1 protein, human) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Proto-Oncogene Proteins c-myb) RN - 0 (Trans-Activators) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Adenoid Cystic/*genetics/pathology MH - Female MH - *Gene Rearrangement MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Neoplasm Grading MH - Oncogene Proteins, Fusion MH - Proto-Oncogene Proteins/*genetics MH - Proto-Oncogene Proteins c-myb/*genetics MH - Salivary Gland Neoplasms/*genetics/pathology MH - Trans-Activators/*genetics MH - Young Adult EDAT- 2018/02/08 06:00 MHDA- 2019/05/21 06:00 CRDT- 2018/02/08 06:00 PHST- 2017/09/26 00:00 [received] PHST- 2017/12/03 00:00 [accepted] PHST- 2017/11/28 00:00 [revised] PHST- 2018/02/08 06:00 [pubmed] PHST- 2019/05/21 06:00 [medline] PHST- 2018/02/08 06:00 [entrez] AID - S0893-3952(22)01494-6 [pii] AID - 10.1038/s41379-018-0008-8 [doi] PST - ppublish SO - Mod Pathol. 2018 Jun;31(6):934-946. doi: 10.1038/s41379-018-0008-8. Epub 2018 Feb 6.