Abstract 2252: Septin 6 in malignant melanoma
Melanoma describes a malignancy of epidermal melanocytes located predominantly in the skin. Melanoma accounts for only 4% of all skin cancers; however, it causes the greatest number of skin cancer-related deaths worldwide. Malignant melanoma is now the seventh most common cancer in the USA. The inci...
Saved in:
Published in | Cancer research (Chicago, Ill.) Vol. 70; no. 8_Supplement; p. 2252 |
---|---|
Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
15.04.2010
|
Online Access | Get full text |
Cover
Loading…
Abstract | Melanoma describes a malignancy of epidermal melanocytes located predominantly in the skin. Melanoma accounts for only 4% of all skin cancers; however, it causes the greatest number of skin cancer-related deaths worldwide. Malignant melanoma is now the seventh most common cancer in the USA. The incidence of melanoma is increasing faster than that of any other human cancer. The sequence of events in which normal melanocytes transform into melanoma cells, referred to as melanomagenesis, is poorly understood. It likely involves a multistep process of progressive genetic mutations which alter cell proliferation and differentiation, and thereby reduce host susceptibility to environmental carcinogens such as ultraviolet radiation.
Septins are an evolutionary conserved family of genes which encode guanosine-5′-triphosphate binding proteins and are involved in a variety of cellular processes, such as cytokinesis, exocytosis, and vesicle trafficking. A total of 14 septin genes have been identified in humans. Septin gene expression is extremely complex, and has been noted to be altered in human neoplasia, infectious diseases and neurological conditions.
Septin 6 (SEPT6) is encoded by a gene on Xq24 and has been implicated in human leukaemia as a fusion partner of MLL. Our laboratory has experimentally shown that the 12 exons of SEPT6 span 85 kbase of Xq24 and undergo complex splicing events such that 7 transcripts (v1-v4***) are produced which encode 5 distinct polypeptides. Of note are 3 discrete transcripts, named v4* to v4***, encoding the same 427 amino acid polypeptide: a phenomenon also seen with SEPT9.
Recent cDNA microarray studies have demonstrated up-regulation of SEPT6 in metastatic melanoma versus primary melanoma, but have only documented pan-SEPT6 expression. But the complexity of septin gene splicing and the limitations of microarray analysis do not allow definition of which splice variants are altered during progression.
We hypothesize that specific SEPT6 splice variants may be associated with the metastatic phenotype of melanoma. We received ethical approval for the extraction of RNA from 300 formalin-fixed, paraffin-embedded skin samples, ranging from benign naevi to both primary and metastatic melanomas. However, RNA retrieved from FFPE tissue is usually of poor quality as it highly degraded. To overcome this phenomenon, we have optimized specific real time quantitative PCR assays, amplifying amplicons of less than 80bp, allowing us to detect each transcript of SEPT6. Several housekeeping genes were initially profiled with β-actin presenting as the most consistently expressed gene and therefore was used as the housekeeping gene in this study. Expression levels of the various SEPT6 transcripts were noted to vary considerably according to clinical subtype.
Our study, which detects each SEPT6 transcript using specific real time quantitative PCR assays, strengthens our hypothesis that particular variants of SEPT6 may be associated with metastatic melanoma.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2252. |
---|---|
AbstractList | Melanoma describes a malignancy of epidermal melanocytes located predominantly in the skin. Melanoma accounts for only 4% of all skin cancers; however, it causes the greatest number of skin cancer-related deaths worldwide. Malignant melanoma is now the seventh most common cancer in the USA. The incidence of melanoma is increasing faster than that of any other human cancer. The sequence of events in which normal melanocytes transform into melanoma cells, referred to as melanomagenesis, is poorly understood. It likely involves a multistep process of progressive genetic mutations which alter cell proliferation and differentiation, and thereby reduce host susceptibility to environmental carcinogens such as ultraviolet radiation.
Septins are an evolutionary conserved family of genes which encode guanosine-5′-triphosphate binding proteins and are involved in a variety of cellular processes, such as cytokinesis, exocytosis, and vesicle trafficking. A total of 14 septin genes have been identified in humans. Septin gene expression is extremely complex, and has been noted to be altered in human neoplasia, infectious diseases and neurological conditions.
Septin 6 (SEPT6) is encoded by a gene on Xq24 and has been implicated in human leukaemia as a fusion partner of MLL. Our laboratory has experimentally shown that the 12 exons of SEPT6 span 85 kbase of Xq24 and undergo complex splicing events such that 7 transcripts (v1-v4***) are produced which encode 5 distinct polypeptides. Of note are 3 discrete transcripts, named v4* to v4***, encoding the same 427 amino acid polypeptide: a phenomenon also seen with SEPT9.
Recent cDNA microarray studies have demonstrated up-regulation of SEPT6 in metastatic melanoma versus primary melanoma, but have only documented pan-SEPT6 expression. But the complexity of septin gene splicing and the limitations of microarray analysis do not allow definition of which splice variants are altered during progression.
We hypothesize that specific SEPT6 splice variants may be associated with the metastatic phenotype of melanoma. We received ethical approval for the extraction of RNA from 300 formalin-fixed, paraffin-embedded skin samples, ranging from benign naevi to both primary and metastatic melanomas. However, RNA retrieved from FFPE tissue is usually of poor quality as it highly degraded. To overcome this phenomenon, we have optimized specific real time quantitative PCR assays, amplifying amplicons of less than 80bp, allowing us to detect each transcript of SEPT6. Several housekeeping genes were initially profiled with β-actin presenting as the most consistently expressed gene and therefore was used as the housekeeping gene in this study. Expression levels of the various SEPT6 transcripts were noted to vary considerably according to clinical subtype.
Our study, which detects each SEPT6 transcript using specific real time quantitative PCR assays, strengthens our hypothesis that particular variants of SEPT6 may be associated with metastatic melanoma.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2252. |
Author | Roche, Muireann Hall, Peter A. Walsh, Maureen Y. Russell, SE Hilary |
Author_xml | – sequence: 1 givenname: Muireann surname: Roche fullname: Roche, Muireann – sequence: 2 givenname: Maureen Y. surname: Walsh fullname: Walsh, Maureen Y. – sequence: 3 givenname: Peter A. surname: Hall fullname: Hall, Peter A. – sequence: 4 givenname: SE Hilary surname: Russell fullname: Russell, SE Hilary |
BookMark | eNqdjk0KwjAUhB9SwfpzAje5QGpe2tjirojixpXuQyypVJq0JNl4exsQD-BmhhkY5ltCYgerAbbIMkRR7VDkFS2LQmT1FRnlXPAZpL82gZQxVlFRlHwBS-9fUxTIRAq0fvjgVBNIHB3ITY-hs2RPJjGq755W2UCM7pUdjFrDvFW915uvryA_n-7HC23c4L3TrRxdZ5R7S2QyksnIICODjGQynuT_rT7udEDf |
ContentType | Journal Article |
DBID | AAYXX CITATION |
DOI | 10.1158/1538-7445.AM10-2252 |
DatabaseName | CrossRef |
DatabaseTitle | CrossRef |
DatabaseTitleList | CrossRef |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Medicine |
EISSN | 1538-7445 |
EndPage | 2252 |
ExternalDocumentID | 10_1158_1538_7445_AM10_2252 |
GroupedDBID | --- -ET 18M 29B 2WC 34G 39C 3O- 476 53G 5GY 5RE 5VS 6J9 AAYXX ABOCM ACGFO ACIWK ACPRK ACSVP ADBBV ADCOW AENEX AFFNX AFHIN AFOSN AFRAH ALMA_UNASSIGNED_HOLDINGS BAWUL BTFSW C1A CITATION CS3 DIK DU5 EBS EJD F5P FRP GX1 H13 IH2 KQ8 L7B LSO OK1 P0W P2P PQQKQ RCR RHF RHI RNS SJN TR2 UDS W2D W8F WH7 WOQ XJT YKV YZZ |
ID | FETCH-crossref_primary_10_1158_1538_7445_AM10_22523 |
ISSN | 0008-5472 |
IngestDate | Thu Nov 21 21:57:50 EST 2024 |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 8_Supplement |
Language | English |
LinkModel | OpenURL |
MergedId | FETCHMERGED-crossref_primary_10_1158_1538_7445_AM10_22523 |
ParticipantIDs | crossref_primary_10_1158_1538_7445_AM10_2252 |
PublicationCentury | 2000 |
PublicationDate | 2010-04-15 |
PublicationDateYYYYMMDD | 2010-04-15 |
PublicationDate_xml | – month: 04 year: 2010 text: 2010-04-15 day: 15 |
PublicationDecade | 2010 |
PublicationTitle | Cancer research (Chicago, Ill.) |
PublicationYear | 2010 |
SSID | ssj0005105 |
Score | 4.002012 |
Snippet | Melanoma describes a malignancy of epidermal melanocytes located predominantly in the skin. Melanoma accounts for only 4% of all skin cancers; however, it... |
SourceID | crossref |
SourceType | Aggregation Database |
StartPage | 2252 |
Title | Abstract 2252: Septin 6 in malignant melanoma |
Volume | 70 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LS8NAEF5qBfEiPvFNDt7iRk03j3oLUilKBduK9RTy2FghTaVNLv4Cf7Yz2c0DLWK9LO3STrKd6WR29ptvCDnTbY6sa4ya_mVEmRVZFKNqylueeRUYLAwZFgr3HszuE7sbGaNG47OGWspSXws-FtaV_EerMAd6xSrZJTRbCoUJeA36hRE0DOOfdOz4mKgIUhX-Ljru7QeIUUlUE7MYE4iwXxHmok547CVT6YArVoKAz1TJ9TPOD3MFKiP3GnGs1XIEfWyrladOsSrMS0qDeoYljkXJT4YAHvVFq1ya7I6MeBvVKef72XwuzzoGHbX7FnsSiCxTD3hqzqgovizdqU0NJnrvaLzyoBYTHJGFixW9QaQp2W7esLRC9kjXqRt67TFcvP3p4g0sWygvozk9uLHqy3VC7W8PuhJ-mG98DNtFIS4KcVGIi0JWyCpSKmIXhvvHinfekGDYYsGSvwqEXCy4k1qMUwtWhptkQ-4yFEeYzBZp8GSbrPUkjmKH0MJyFBR0rQi7UUwFhtJulMJudknrtjO86dLicu674Chxf1lia480k2nC94kStgMriixw3F7EGA890488WB-_bOsWRMoH5HwZyYfLffyIrFdWdUya6SzjJxDipf5p_ut_AW2GR-c |
link.rule.ids | 314,780,784,27924,27925 |
linkProvider | Colorado Alliance of Research Libraries |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Abstract+2252%3A+Septin+6+in+malignant+melanoma&rft.jtitle=Cancer+research+%28Chicago%2C+Ill.%29&rft.au=Roche%2C+Muireann&rft.au=Walsh%2C+Maureen+Y.&rft.au=Hall%2C+Peter+A.&rft.au=Russell%2C+SE+Hilary&rft.date=2010-04-15&rft.issn=0008-5472&rft.eissn=1538-7445&rft.volume=70&rft.issue=8_Supplement&rft.spage=2252&rft.epage=2252&rft_id=info:doi/10.1158%2F1538-7445.AM10-2252&rft.externalDBID=n%2Fa&rft.externalDocID=10_1158_1538_7445_AM10_2252 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0008-5472&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0008-5472&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0008-5472&client=summon |