PMID- 35982173
OWN - NLM
STAT- MEDLINE
DCOM- 20220822
LR  - 20220823
IS  - 2399-3642 (Electronic)
IS  - 2399-3642 (Linking)
VI  - 5
IP  - 1
DP  - 2022 Aug 18
TI  - Differential ion mobility mass spectrometry in immunopeptidomics identifies 
      neoantigens carrying colorectal cancer driver mutations.
PG  - 831
LID - 10.1038/s42003-022-03807-w [doi]
LID - 831
AB  - Understanding the properties of human leukocyte antigen (HLA) peptides 
      (immunopeptides) is essential for precision cancer medicine, while the direct 
      identification of immunopeptides from small biopsies of clinical tissues by mass 
      spectrometry (MS) is still confronted with technical challenges. Here, to 
      overcome these hindrances, high-field asymmetric waveform ion mobility 
      spectrometry (FAIMS) is introduced to conduct differential ion mobility (DIM)-MS 
      by seamless gas-phase fractionation optimal for scarce samples. By established 
      DIM-MS for immunopeptidomics analysis, on average, 42.9 mg of normal and tumor 
      colorectal tissues from identical patients (n = 17) were analyzed, and on average 
      4921 immunopeptides were identified. Among these 44,815 unique immunopeptides, 
      two neoantigens, KRAS-G12V and CPPED1-R228Q, were identified. These neoantigens 
      were confirmed by synthetic peptides through targeted MS in parallel reaction 
      monitoring (PRM) mode. Comparison of the tissue-based personal immunopeptidome 
      revealed tumor-specific processing of immunopeptides. Since the direct 
      identification of neoantigens from tumor tissues suggested that more potential 
      neoantigens have yet to be identified, we screened cell lines with known 
      oncogenic KRAS mutations and identified 2 more neoantigens that carry KRAS-G12V. 
      These results indicated that the established FAIMS-assisted DIM-MS is effective 
      in the identification of immunopeptides and potential recurrent neoantigens 
      directly from scarce samples such as clinical tissues.
CI  - (c) 2022. The Author(s).
FAU - Minegishi, Yuriko
AU  - Minegishi Y
AD  - Cancer Proteomics Group, Cancer Precision Medicine Center, Japanese Foundation 
      for Cancer Research, Tokyo, Japan.
FAU - Kiyotani, Kazuma
AU  - Kiyotani K
AUID- ORCID: 0000-0002-9236-9061
AD  - Project for Immunogenomics, Cancer Precision Medicine Center, Japanese Foundation 
      for Cancer Research, Tokyo, Japan.
FAU - Nemoto, Kensaku
AU  - Nemoto K
AD  - Project for Immunogenomics, Cancer Precision Medicine Center, Japanese Foundation 
      for Cancer Research, Tokyo, Japan.
FAU - Inoue, Yoshikage
AU  - Inoue Y
AD  - Department of Surgery, Kyoto University, Kyoto, Japan.
FAU - Haga, Yoshimi
AU  - Haga Y
AUID- ORCID: 0000-0001-7861-617X
AD  - Cancer Proteomics Group, Cancer Precision Medicine Center, Japanese Foundation 
      for Cancer Research, Tokyo, Japan.
FAU - Fujii, Risa
AU  - Fujii R
AD  - Cancer Proteomics Group, Cancer Precision Medicine Center, Japanese Foundation 
      for Cancer Research, Tokyo, Japan.
FAU - Saichi, Naomi
AU  - Saichi N
AD  - Cancer Proteomics Group, Cancer Precision Medicine Center, Japanese Foundation 
      for Cancer Research, Tokyo, Japan.
FAU - Nagayama, Satoshi
AU  - Nagayama S
AD  - Development of Gastroenterological Surgery, Cancer Institute Hospital of Japanese 
      Foundation for Cancer Research, Tokyo, Japan.
FAU - Ueda, Koji
AU  - Ueda K
AUID- ORCID: 0000-0001-9066-4959
AD  - Cancer Proteomics Group, Cancer Precision Medicine Center, Japanese Foundation 
      for Cancer Research, Tokyo, Japan. koji.ueda@jfcr.or.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220818
PL  - England
TA  - Commun Biol
JT  - Communications biology
JID - 101719179
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Peptides)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - *Colorectal Neoplasms/genetics
MH  - Histocompatibility Antigens Class I
MH  - Humans
MH  - *Ion Mobility Spectrometry/methods
MH  - Mass Spectrometry/methods
MH  - Mutation
MH  - Peptides/chemistry
MH  - Proto-Oncogene Proteins p21(ras)/genetics
PMC - PMC9388627
COIS- The authors declare no competing interests.
EDAT- 2022/08/19 06:00
MHDA- 2022/08/23 06:00
PMCR- 2022/08/18
CRDT- 2022/08/18 23:26
PHST- 2021/10/27 00:00 [received]
PHST- 2022/08/05 00:00 [accepted]
PHST- 2022/08/18 23:26 [entrez]
PHST- 2022/08/19 06:00 [pubmed]
PHST- 2022/08/23 06:00 [medline]
PHST- 2022/08/18 00:00 [pmc-release]
AID - 10.1038/s42003-022-03807-w [pii]
AID - 3807 [pii]
AID - 10.1038/s42003-022-03807-w [doi]
PST - epublish
SO  - Commun Biol. 2022 Aug 18;5(1):831. doi: 10.1038/s42003-022-03807-w.