* 164850

MYCL PROTOONCOGENE, bHLH TRANSCRIPTION FACTOR; MYCL


Alternative titles; symbols

V-MYC AVIAN MYELOCYTOMATOSIS VIRAL ONCOGENE HOMOLOG, LUNG CARCINOMA-DERIVED
V-MYC AVIAN MYELOCYTOMATOSIS VIRAL ONCOGENE HOMOLOG 1, LUNG CARCINOMA-DERIVED; MYCL1
AVIAN MYELOCYTOMATOSIS VIRAL ONCOGENE HOMOLOG 1, LUNG CARCINOMA-DERIVED
ONCOGENE LMYC
MYC-RELATED GENE FROM LUNG CANCER


HGNC Approved Gene Symbol: MYCL

Cytogenetic location: 1p34.2     Genomic coordinates (GRCh38): 1:39,895,428-39,901,917 (from NCBI)


TEXT

Cloning and Expression

Nau et al. (1985) cloned from DNA of small-cell lung cancer (SCCL) a gene, designated LMYC, with homology to a small region of both MYC (190080) and NMYC (164840). This LMYC sequence was amplified 10- to 20-fold in the DNA of 4 SCCL lines and of 1 SCCL specimen taken directly from a patient. A restriction polymorphism was found. In heterozygotes, only 1 of the 2 alleles was amplified in any 1 genome.

Kaye et al. (1988) found that several distinct mRNAs were produced in all SCCL cell lines that expressed LMYC. These transcripts were generated from a single gene by alternative splicing of introns 1 and 2 and by use of alternative polyadenylation signals. Comparisons with MYC and NMYC demonstrated multiple discrete regions with extensive homology.


Gene Function

To examine the in vivo function of Mycl1 in mice, Kc et al. (2014) generated an inactivating Mycl1-GFP allele that also reports Mycl1 expression. Kc et al. (2014) found that Mycl1 is selectively expressed in dendritic cells of the immune system and controlled by IRF8 (601565), and that during dendritic cell development, Mycl1 expression is initiated in the common dendritic cell progenitor concurrent with reduction in c-Myc expression. Mature dendritic cells lack expression of c-Myc and N-Myc (MYCN; 164840) but maintain L-Myc (MYCL; 164850) expression even in the presence of inflammatory signals such as granulocyte-macrophage colony-stimulating factor (GMCSF; 138960). All dendritic cell subsets developed in Mycl1-deficient mice, but some subsets such as migratory CD103 (604682)-positive conventional dendritic cells in the lung and liver were greatly reduced at steady state. Importantly, loss of L-Myc by dendritic cells caused a significant decrease in in vivo T-cell priming during infection by Listeria monocytogenes and vesicular stomatitis virus. Kc et al. (2014) concluded that the replacement of c-Myc by L-Myc in immature dendritic cells may provide for Myc transcriptional activity in the setting of inflammation that is required for optimal T-cell priming.


Gene Structure

Kaye et al. (1988) found that the LMYC gene contains 3 exons and spans 6.6 kilobases.


Mapping

By somatic cell hybridization and in situ hybridization, Nau et al. (1985) assigned the LMYC gene to chromosome 1p32.

In a linkage map of chromosome 1 prepared by Rouleau et al. (1990), it was concluded that MYCL1 is 17 cM proximal to RH.

When studying chromosome 1p breakpoints in neuroblastoma cell lines using fluorescence in situ hybridization (FISH) with region-specific probes, Van Roy et al. (1995) found evidence for a position of MYCL1 more distal than 1p32. To investigate the discrepancy, Speleman et al. (1996) used FISH on high-resolution R-banded chromosomes with a YAC clone for MYCL1 and reassigned the gene to 1p34.3.

By study of DNA from mouse-hamster somatic cell hybrids, Campbell et al. (1989) mapped 2 Lmyc loci provisionally to mouse chromosomes 4 and 12. The locus on chromosome 12 may be a pseudogene.


Molecular Genetics

Kawashima et al. (1988) concluded that a correlation exists between particular RFLP alleles of the MYCL gene and the occurrence of metastasis of lung cancer to lymph nodes and other organs. Among lung cancer patients, those with only the L band (10 kb) had few lymph node metastases, whereas patients with either the S band (6 kb) or the S and L bands almost always had lymph node metastases. A similar correlation was found between the presence of the S band and metastases to other organs. The correlation was particularly marked in cases of adenocarcinoma of the lung.


See Also:

REFERENCES

  1. Campbell, G. R., Zimmerman, K., Blank, R. D., Alt, F. W., D'Eustachio, P. Chromosomal location of N-myc and L-myc genes in the mouse. Oncogene Res. 4: 47-54, 1989. [PubMed: 2654812, related citations]

  2. Kawashima, K., Shikama, H., Imoto, K., Izawa, M., Naruke, T., Okabayashi, K., Nishimura, S. Close correlation between restriction fragment length polymorphism of the L-MYC gene and metastasis of human lung cancer to the lymph nodes and other organs. Proc. Nat. Acad. Sci. 85: 2353-2356, 1988. [PubMed: 2895475, related citations] [Full Text]

  3. Kaye, F., Battey, J., Nau, M., Brooks, B., Seifter, E., De Greve, J., Birrer, M., Sausville, E., Minna, J. Structure and expression of the human L-myc gene reveal a complex pattern of alternative mRNA processing. Molec. Cell. Biol. 8: 186-195, 1988. [PubMed: 2827002, related citations] [Full Text]

  4. Kc, W., Satpathy, A. T., Rapaport, A. S., Briseno, C. G., Wu, X., Albring, J. C., Russler-Germain, E. V., Kretzer, N. M., Durai, V., Persaud, S. P., Edelson, B. T., Loschko, J., Cella, M., Allen, P. M., Nussenzweig, M. C., Colonna, M., Sleckman, B. P., Murphy, T. L., Murphy, K. M. L-Myc expression by dendritic cells is required for optimal T-cell priming. Nature 507: 243-247, 2014. [PubMed: 24509714, images, related citations] [Full Text]

  5. McBride, O. W., Kirsch, I., Hollis, G., Nau, M., Battey, J., Minna, J. Human L-myc (MYCL) proto-oncogene is on chromosome 1p32. (Abstract) Cytogenet. Cell Genet. 40: 694 only, 1985.

  6. Nau, M. M., Brooks, B. J., Battey, J., Sausville, E., Gazdar, A. F., Kirsch, I. R., McBride, O. W., Bertness, V., Hollis, G. F., Minna, J. D. L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. Nature 318: 69-73, 1985. [PubMed: 2997622, related citations] [Full Text]

  7. Rouleau, G. A., Bazanowski, A., Gusella, J. F., Haines, J. L. A genetic map of chromosome 1: comparison of different data sets and linkage programs. Genomics 7: 313-318, 1990. [PubMed: 2365352, related citations] [Full Text]

  8. Speleman, F., Van Camp, G., Van Roy, N. Reassignment of MYCL1 to human chromosome 1p34.3 by fluorescence in situ hybridization. Cytogenet. Cell Genet. 72: 189-190, 1996. [PubMed: 8978772, related citations] [Full Text]

  9. Van Roy, N., Cheng, N. C., Laureys, G., Opdenakker, G., Versteeg, R., Speleman, F. Molecular cytogenetic analysis of 1;17 translocations in neuroblastoma. Europ. J. Cancer 31A: 530-535, 1995. [PubMed: 7576960, related citations] [Full Text]


Contributors:
Ada Hamosh - updated : 4/17/2014
Creation Date:
Victor A. McKusick : 6/2/1986
carol : 01/07/2020
carol : 01/06/2020
alopez : 04/17/2014
alopez : 4/17/2014
carol : 1/24/2014
alopez : 9/3/1998
terry : 6/13/1996
terry : 6/7/1996
carol : 11/12/1993
supermim : 3/16/1992
carol : 7/5/1990
supermim : 3/20/1990
ddp : 10/27/1989
root : 7/7/1989

* 164850

MYCL PROTOONCOGENE, bHLH TRANSCRIPTION FACTOR; MYCL


Alternative titles; symbols

V-MYC AVIAN MYELOCYTOMATOSIS VIRAL ONCOGENE HOMOLOG, LUNG CARCINOMA-DERIVED
V-MYC AVIAN MYELOCYTOMATOSIS VIRAL ONCOGENE HOMOLOG 1, LUNG CARCINOMA-DERIVED; MYCL1
AVIAN MYELOCYTOMATOSIS VIRAL ONCOGENE HOMOLOG 1, LUNG CARCINOMA-DERIVED
ONCOGENE LMYC
MYC-RELATED GENE FROM LUNG CANCER


HGNC Approved Gene Symbol: MYCL

Cytogenetic location: 1p34.2     Genomic coordinates (GRCh38): 1:39,895,428-39,901,917 (from NCBI)


TEXT

Cloning and Expression

Nau et al. (1985) cloned from DNA of small-cell lung cancer (SCCL) a gene, designated LMYC, with homology to a small region of both MYC (190080) and NMYC (164840). This LMYC sequence was amplified 10- to 20-fold in the DNA of 4 SCCL lines and of 1 SCCL specimen taken directly from a patient. A restriction polymorphism was found. In heterozygotes, only 1 of the 2 alleles was amplified in any 1 genome.

Kaye et al. (1988) found that several distinct mRNAs were produced in all SCCL cell lines that expressed LMYC. These transcripts were generated from a single gene by alternative splicing of introns 1 and 2 and by use of alternative polyadenylation signals. Comparisons with MYC and NMYC demonstrated multiple discrete regions with extensive homology.


Gene Function

To examine the in vivo function of Mycl1 in mice, Kc et al. (2014) generated an inactivating Mycl1-GFP allele that also reports Mycl1 expression. Kc et al. (2014) found that Mycl1 is selectively expressed in dendritic cells of the immune system and controlled by IRF8 (601565), and that during dendritic cell development, Mycl1 expression is initiated in the common dendritic cell progenitor concurrent with reduction in c-Myc expression. Mature dendritic cells lack expression of c-Myc and N-Myc (MYCN; 164840) but maintain L-Myc (MYCL; 164850) expression even in the presence of inflammatory signals such as granulocyte-macrophage colony-stimulating factor (GMCSF; 138960). All dendritic cell subsets developed in Mycl1-deficient mice, but some subsets such as migratory CD103 (604682)-positive conventional dendritic cells in the lung and liver were greatly reduced at steady state. Importantly, loss of L-Myc by dendritic cells caused a significant decrease in in vivo T-cell priming during infection by Listeria monocytogenes and vesicular stomatitis virus. Kc et al. (2014) concluded that the replacement of c-Myc by L-Myc in immature dendritic cells may provide for Myc transcriptional activity in the setting of inflammation that is required for optimal T-cell priming.


Gene Structure

Kaye et al. (1988) found that the LMYC gene contains 3 exons and spans 6.6 kilobases.


Mapping

By somatic cell hybridization and in situ hybridization, Nau et al. (1985) assigned the LMYC gene to chromosome 1p32.

In a linkage map of chromosome 1 prepared by Rouleau et al. (1990), it was concluded that MYCL1 is 17 cM proximal to RH.

When studying chromosome 1p breakpoints in neuroblastoma cell lines using fluorescence in situ hybridization (FISH) with region-specific probes, Van Roy et al. (1995) found evidence for a position of MYCL1 more distal than 1p32. To investigate the discrepancy, Speleman et al. (1996) used FISH on high-resolution R-banded chromosomes with a YAC clone for MYCL1 and reassigned the gene to 1p34.3.

By study of DNA from mouse-hamster somatic cell hybrids, Campbell et al. (1989) mapped 2 Lmyc loci provisionally to mouse chromosomes 4 and 12. The locus on chromosome 12 may be a pseudogene.


Molecular Genetics

Kawashima et al. (1988) concluded that a correlation exists between particular RFLP alleles of the MYCL gene and the occurrence of metastasis of lung cancer to lymph nodes and other organs. Among lung cancer patients, those with only the L band (10 kb) had few lymph node metastases, whereas patients with either the S band (6 kb) or the S and L bands almost always had lymph node metastases. A similar correlation was found between the presence of the S band and metastases to other organs. The correlation was particularly marked in cases of adenocarcinoma of the lung.


See Also:

McBride et al. (1985)

REFERENCES

  1. Campbell, G. R., Zimmerman, K., Blank, R. D., Alt, F. W., D'Eustachio, P. Chromosomal location of N-myc and L-myc genes in the mouse. Oncogene Res. 4: 47-54, 1989. [PubMed: 2654812]

  2. Kawashima, K., Shikama, H., Imoto, K., Izawa, M., Naruke, T., Okabayashi, K., Nishimura, S. Close correlation between restriction fragment length polymorphism of the L-MYC gene and metastasis of human lung cancer to the lymph nodes and other organs. Proc. Nat. Acad. Sci. 85: 2353-2356, 1988. [PubMed: 2895475] [Full Text: https://doi.org/10.1073/pnas.85.7.2353]

  3. Kaye, F., Battey, J., Nau, M., Brooks, B., Seifter, E., De Greve, J., Birrer, M., Sausville, E., Minna, J. Structure and expression of the human L-myc gene reveal a complex pattern of alternative mRNA processing. Molec. Cell. Biol. 8: 186-195, 1988. [PubMed: 2827002] [Full Text: https://doi.org/10.1128/mcb.8.1.186-195.1988]

  4. Kc, W., Satpathy, A. T., Rapaport, A. S., Briseno, C. G., Wu, X., Albring, J. C., Russler-Germain, E. V., Kretzer, N. M., Durai, V., Persaud, S. P., Edelson, B. T., Loschko, J., Cella, M., Allen, P. M., Nussenzweig, M. C., Colonna, M., Sleckman, B. P., Murphy, T. L., Murphy, K. M. L-Myc expression by dendritic cells is required for optimal T-cell priming. Nature 507: 243-247, 2014. [PubMed: 24509714] [Full Text: https://doi.org/10.1038/nature12967]

  5. McBride, O. W., Kirsch, I., Hollis, G., Nau, M., Battey, J., Minna, J. Human L-myc (MYCL) proto-oncogene is on chromosome 1p32. (Abstract) Cytogenet. Cell Genet. 40: 694 only, 1985.

  6. Nau, M. M., Brooks, B. J., Battey, J., Sausville, E., Gazdar, A. F., Kirsch, I. R., McBride, O. W., Bertness, V., Hollis, G. F., Minna, J. D. L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. Nature 318: 69-73, 1985. [PubMed: 2997622] [Full Text: https://doi.org/10.1038/318069a0]

  7. Rouleau, G. A., Bazanowski, A., Gusella, J. F., Haines, J. L. A genetic map of chromosome 1: comparison of different data sets and linkage programs. Genomics 7: 313-318, 1990. [PubMed: 2365352] [Full Text: https://doi.org/10.1016/0888-7543(90)90163-o]

  8. Speleman, F., Van Camp, G., Van Roy, N. Reassignment of MYCL1 to human chromosome 1p34.3 by fluorescence in situ hybridization. Cytogenet. Cell Genet. 72: 189-190, 1996. [PubMed: 8978772] [Full Text: https://doi.org/10.1159/000134185]

  9. Van Roy, N., Cheng, N. C., Laureys, G., Opdenakker, G., Versteeg, R., Speleman, F. Molecular cytogenetic analysis of 1;17 translocations in neuroblastoma. Europ. J. Cancer 31A: 530-535, 1995. [PubMed: 7576960] [Full Text: https://doi.org/10.1016/0959-8049(95)00004-3]


Contributors:
Ada Hamosh - updated : 4/17/2014

Creation Date:
Victor A. McKusick : 6/2/1986

Edit History:
carol : 01/07/2020
carol : 01/06/2020
alopez : 04/17/2014
alopez : 4/17/2014
carol : 1/24/2014
alopez : 9/3/1998
terry : 6/13/1996
terry : 6/7/1996
carol : 11/12/1993
supermim : 3/16/1992
carol : 7/5/1990
supermim : 3/20/1990
ddp : 10/27/1989
root : 7/7/1989