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A catalog of HLA type, HLA expression, and neo-epitope candidates in human cancer cell lines.

Boegel S, Löwer M, Bukur T, Sahin U, Castle JC - Oncoimmunology (2014)

Bottom Line: First, we present previously unreported HLA Class I and II genotypes.Third, using these results, we provide a fundamental cell line "barcode" to track samples and prevent sample annotation swaps and contamination.The compilation of our results are a fundamental resource for all researchers selecting specific cancer cell lines based on the HLA type and HLA expression, as well as for the development of immunotherapeutic tools for novel cancer treatment modalities.

View Article: PubMed Central - PubMed

Affiliation: TRON gGmbH - Translational Oncology at Johannes Gutenberg-University Medical Center gGmbH ; Langenbeckstr; Mainz, Germany ; University Medical Center of the Johannes Gutenberg-University Mainz ; Mainz, Germany.

ABSTRACT

Cancer cell lines are a tremendous resource for cancer biology and therapy development. These multipurpose tools are commonly used to examine the genetic origin of cancers, to identify potential novel tumor targets, such as tumor antigens for vaccine devel-opment, and utilized to screen potential therapies in preclinical studies. Mutations, gene expression, and drug sensitivity have been determined for many cell lines using next-generation sequencing (NGS). However, the human leukocyte antigen (HLA) type and HLA expression of tumor cell lines, characterizations necessary for the development of cancer vaccines, have remained largely incomplete and, such information, when available, has been distributed in many publications. Here, we determine the 4-digit HLA type and HLA expression of 167 cancer and 10 non-cancer cell lines from publically available RNA-Seq data. We use standard NGS RNA-Seq short reads from "whole transcriptome" sequencing, map reads to known HLA types, and statistically determine HLA type, heterozygosity, and expression. First, we present previously unreported HLA Class I and II genotypes. Second, we determine HLA expression levels in each cancer cell line, providing insights into HLA downregulation and loss in cancer. Third, using these results, we provide a fundamental cell line "barcode" to track samples and prevent sample annotation swaps and contamination. Fourth, we integrate the cancer cell-line specific HLA types and HLA expression with available cell-line specific mutation information and existing HLA binding prediction algorithms to make a catalog of predicted antigenic mutations in each cell line. The compilation of our results are a fundamental resource for all researchers selecting specific cancer cell lines based on the HLA type and HLA expression, as well as for the development of immunotherapeutic tools for novel cancer treatment modalities.

No MeSH data available.


Related in: MedlinePlus

HLA expression profiles of 167 cancer cell lines grouped according to the tissue/disease of origin. The 167 cancer cell lines analyzed in the study are grouped according to their cancer type and each point represents the HLA expression level in one distinct cell line and in cases of replicate RNA-Seq datasets (for 45 cell lines), a point represents the mean expression value of the respective cell line. (red) and SEM (gray) is plotted for HLA Class I (A) and HLA Class II (B). HLA Class I expression is defined as the sum of individual reads for each HLA-A, HLA-B and HLA-C and HLA Class II expression is defined as the sum of individual reads for HLA-DQA1, HLA-DQB1, HLA-DRB1.RPKM, reads per kilobase of exon model per million mapped reads.
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f0003: HLA expression profiles of 167 cancer cell lines grouped according to the tissue/disease of origin. The 167 cancer cell lines analyzed in the study are grouped according to their cancer type and each point represents the HLA expression level in one distinct cell line and in cases of replicate RNA-Seq datasets (for 45 cell lines), a point represents the mean expression value of the respective cell line. (red) and SEM (gray) is plotted for HLA Class I (A) and HLA Class II (B). HLA Class I expression is defined as the sum of individual reads for each HLA-A, HLA-B and HLA-C and HLA Class II expression is defined as the sum of individual reads for HLA-DQA1, HLA-DQB1, HLA-DRB1.RPKM, reads per kilobase of exon model per million mapped reads.

Mentions: In general, we observed moderate to high HLA Class I expression throughout the different tissues/disease-groups (Fig. 3). Ovarian and prostate cancer cell lines and K-562 show no or very low levels. HLA Class II is absent in almost all tissue/disease groups, with the exceptions of Burkitt lymphoma, mantle cell lymphoma and melanoma cell lines (Fig. 3). Of the 167 cancer cell lines, 39 (23%) showed no or very weak expression (less than 1 RPKM) for at least one HLA Class I and 136 (82%) showed no or very weak expression for at least one HLA Class II locus.Figure 2.


A catalog of HLA type, HLA expression, and neo-epitope candidates in human cancer cell lines.

Boegel S, Löwer M, Bukur T, Sahin U, Castle JC - Oncoimmunology (2014)

HLA expression profiles of 167 cancer cell lines grouped according to the tissue/disease of origin. The 167 cancer cell lines analyzed in the study are grouped according to their cancer type and each point represents the HLA expression level in one distinct cell line and in cases of replicate RNA-Seq datasets (for 45 cell lines), a point represents the mean expression value of the respective cell line. (red) and SEM (gray) is plotted for HLA Class I (A) and HLA Class II (B). HLA Class I expression is defined as the sum of individual reads for each HLA-A, HLA-B and HLA-C and HLA Class II expression is defined as the sum of individual reads for HLA-DQA1, HLA-DQB1, HLA-DRB1.RPKM, reads per kilobase of exon model per million mapped reads.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4355981&req=5

f0003: HLA expression profiles of 167 cancer cell lines grouped according to the tissue/disease of origin. The 167 cancer cell lines analyzed in the study are grouped according to their cancer type and each point represents the HLA expression level in one distinct cell line and in cases of replicate RNA-Seq datasets (for 45 cell lines), a point represents the mean expression value of the respective cell line. (red) and SEM (gray) is plotted for HLA Class I (A) and HLA Class II (B). HLA Class I expression is defined as the sum of individual reads for each HLA-A, HLA-B and HLA-C and HLA Class II expression is defined as the sum of individual reads for HLA-DQA1, HLA-DQB1, HLA-DRB1.RPKM, reads per kilobase of exon model per million mapped reads.
Mentions: In general, we observed moderate to high HLA Class I expression throughout the different tissues/disease-groups (Fig. 3). Ovarian and prostate cancer cell lines and K-562 show no or very low levels. HLA Class II is absent in almost all tissue/disease groups, with the exceptions of Burkitt lymphoma, mantle cell lymphoma and melanoma cell lines (Fig. 3). Of the 167 cancer cell lines, 39 (23%) showed no or very weak expression (less than 1 RPKM) for at least one HLA Class I and 136 (82%) showed no or very weak expression for at least one HLA Class II locus.Figure 2.

Bottom Line: First, we present previously unreported HLA Class I and II genotypes.Third, using these results, we provide a fundamental cell line "barcode" to track samples and prevent sample annotation swaps and contamination.The compilation of our results are a fundamental resource for all researchers selecting specific cancer cell lines based on the HLA type and HLA expression, as well as for the development of immunotherapeutic tools for novel cancer treatment modalities.

View Article: PubMed Central - PubMed

Affiliation: TRON gGmbH - Translational Oncology at Johannes Gutenberg-University Medical Center gGmbH ; Langenbeckstr; Mainz, Germany ; University Medical Center of the Johannes Gutenberg-University Mainz ; Mainz, Germany.

ABSTRACT

Cancer cell lines are a tremendous resource for cancer biology and therapy development. These multipurpose tools are commonly used to examine the genetic origin of cancers, to identify potential novel tumor targets, such as tumor antigens for vaccine devel-opment, and utilized to screen potential therapies in preclinical studies. Mutations, gene expression, and drug sensitivity have been determined for many cell lines using next-generation sequencing (NGS). However, the human leukocyte antigen (HLA) type and HLA expression of tumor cell lines, characterizations necessary for the development of cancer vaccines, have remained largely incomplete and, such information, when available, has been distributed in many publications. Here, we determine the 4-digit HLA type and HLA expression of 167 cancer and 10 non-cancer cell lines from publically available RNA-Seq data. We use standard NGS RNA-Seq short reads from "whole transcriptome" sequencing, map reads to known HLA types, and statistically determine HLA type, heterozygosity, and expression. First, we present previously unreported HLA Class I and II genotypes. Second, we determine HLA expression levels in each cancer cell line, providing insights into HLA downregulation and loss in cancer. Third, using these results, we provide a fundamental cell line "barcode" to track samples and prevent sample annotation swaps and contamination. Fourth, we integrate the cancer cell-line specific HLA types and HLA expression with available cell-line specific mutation information and existing HLA binding prediction algorithms to make a catalog of predicted antigenic mutations in each cell line. The compilation of our results are a fundamental resource for all researchers selecting specific cancer cell lines based on the HLA type and HLA expression, as well as for the development of immunotherapeutic tools for novel cancer treatment modalities.

No MeSH data available.


Related in: MedlinePlus