HAEM5:Sezary syndrome - Revision history

Bailey.Glen at 17:29, 3 July 2025

2025-07-03T17:29:28Z

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	~~==WHO Essential and Desirable Genetic Diagnostic Criteria==~~
	<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
	~~{\| class="wikitable"~~
	\|+
	\|WHO Essential Criteria (Genetics)*
	\|
	\|-
	\|WHO Desirable Criteria (Genetics)*
	\|
	\|-
	~~\|Other Classification~~
	\|
	\|}
	<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
	==Related Terminology==		==Related Terminology==

Bailey.Glen at 21:48, 25 May 2025

2025-05-25T21:48:54Z

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	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
	!Chr #!!~~'''~~Gain, Loss, Amp, LOH~~'''~~!!~~'''~~Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]~~'''~~!!~~'''~~Relevant Gene(s)~~'''~~		!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
	!~~'''~~Diagnostic, Prognostic, and Therapeutic Significance - D, P, T~~'''~~		!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
	!~~'''~~Established Clinical Significance Per Guidelines - Yes or No (Source)~~'''~~		!Established Clinical Significance Per Guidelines - Yes or No (Source)
	!~~'''~~Clinical Relevance Details/Other Notes~~'''~~		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|<span class="blue-text">EXAMPLE:</span>		\|<span class="blue-text">EXAMPLE:</span>
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	!Chromosomal Pattern		!Chromosomal Pattern
	!Molecular Pathogenesis		!Molecular Pathogenesis
	!~~'''~~Prevalence -~~'''~~		!Prevalence -
	~~'''~~Common >20%, Recurrent 5-20% or Rare <5% (Disease)~~'''~~		Common >20%, Recurrent 5-20% or Rare <5% (Disease)
	!~~'''~~Diagnostic, Prognostic, and Therapeutic Significance - D, P, T~~'''~~		!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
	!~~'''~~Established Clinical Significance Per Guidelines - Yes or No (Source)~~'''~~		!Established Clinical Significance Per Guidelines - Yes or No (Source)
	!~~'''~~Clinical Relevance Details/Other Notes~~'''~~		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|<span class="blue-text">EXAMPLE:</span>		\|<span class="blue-text">EXAMPLE:</span>
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	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
	!Gene!!~~'''~~Genetic Alteration~~'''~~!!~~'''~~Tumor Suppressor Gene, Oncogene, Other~~'''~~!!~~'''~~Prevalence -~~'''~~		!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
	~~'''~~Common >20%, Recurrent 5-20% or Rare <5% (Disease)~~'''~~		Common >20%, Recurrent 5-20% or Rare <5% (Disease)
	!~~'''~~Diagnostic, Prognostic, and Therapeutic Significance - D, P, T ~~'''~~		!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
	!~~'''~~Established Clinical Significance Per Guidelines - Yes or No (Source)~~'''~~		!Established Clinical Significance Per Guidelines - Yes or No (Source)
	!~~'''~~Clinical Relevance Details/Other Notes~~'''~~		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|<span class="blue-text">EXAMPLE:</span>''EGFR''		\|<span class="blue-text">EXAMPLE:</span>''EGFR''

Bailey.Glen at 20:25, 25 May 2025

2025-05-25T20:25:16Z

← Older revision		Revision as of 15:25, 25 May 2025
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	<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].		<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
	==Related Terminology==		==Related Terminology==
	~~<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>~~
	{\| class="wikitable"		{\| class="wikitable"
	\|+		\|+
	\|Acceptable		\|Acceptable
	\|		\|N/A
	\|-		\|-
	\|Not Recommended		\|Not Recommended
	\|		\|N/A
	\|}		\|}

Bailey.Glen at 17:45, 24 March 2025

2025-03-24T17:45:49Z

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	{{DISPLAYTITLE:Sezary syndrome}}		{{DISPLAYTITLE:Sezary syndrome}}

	[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]		[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]

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	Daynna J. Wolff, PhD, Medical University of South Carolina		Daynna J. Wolff, PhD, Medical University of South Carolina

	~~__TOC__~~

	==WHO Classification of Disease==		==WHO Classification of Disease==

Jennelleh at 11:26, 19 February 2025

2025-02-19T11:26:54Z

← Older revision		Revision as of 06:26, 19 February 2025
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	Balanced translocations have not been detected in SS<ref name=":0">1. Arber DA, et al., (2017). Sézary syndrome, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4<sup>th</sup> edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p390-391. </ref>.		Balanced translocations have not been detected in SS<ref name=":0">1. Arber DA, et al., (2017). Sézary syndrome, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4<sup>th</sup> edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p390-391. </ref>.

	Gene fusion between CTLA4 and CD28 is highly expressed. Additional fusion events include TYK2-UPF1, COL25A1-NFKB2, FASN-SGMS1, SMS1-ZEB1, SPATA21-RASA2, PITRM1-HK1, and BCR-NDUFAF6<ref name=":2">{{Cite journal~~\|displayauthors=1~~\|last=Prasad\|first=Aparna\|date=2016\|title=Identification of Gene Mutations and Fusion Genes in Patients with ~~Sezary~~ Syndrome\|url=\|journal=Journal of Investigative Dermatology\|volume=136\|pages=\|~~via~~=}}</ref>.		Gene fusion between CTLA4 and CD28 is highly expressed. Additional fusion events include TYK2-UPF1, COL25A1-NFKB2, FASN-SGMS1, SMS1-ZEB1, SPATA21-RASA2, PITRM1-HK1, and BCR-NDUFAF6<ref name=":1">{{Cite journal\|last=Prasad\|first=Aparna\|last2=Rabionet\|first2=Raquel\|last3=Espinet\|first3=Blanca\|last4=Zapata\|first4=Luis\|last5=Puiggros\|first5=Anna\|last6=Melero\|first6=Carme\|last7=Puig\|first7=Anna\|last8=Sarria-Trujillo\|first8=Yaris\|last9=Ossowski\|first9=Stephan\|date=2016-07\|title=Identification of Gene Mutations and Fusion Genes in Patients with Sézary Syndrome\|url=https://pubmed.ncbi.nlm.nih.gov/27039262\|journal=The Journal of Investigative Dermatology\|volume=136\|issue=7\|pages=1490–1499\|doi=10.1016/j.jid.2016.03.024\|issn=1523-1747\|pmid=27039262}}</ref>.

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	* Gene Mutations (SNV/INDEL)}}</blockquote>		* Gene Mutations (SNV/INDEL)}}</blockquote>

	SS is aggressive; however, prognosis is variable and largely depends on stage. A median survival of 32 months and a 5-year survival rate of 10-30% has been reported <ref name=":0" />. Death usually results from opportunistic infections, as SS patients are at an increased risk for infection due to underlying immune dysfunction<ref name=":1">1. Rook, AH and Olsen, EA. Clinical presentation, pathologic features, and Diagnosis of Sézary syndrome. UpToDate. Uptodate.com. Last updated: June 24, 2020. Date accessed: January 29, 2021. </~~ref~~>. Lymph node and visceral involvement are poor prognostic factors, as is the degree of peripheral blood involvement by Sézary cells. Bone marrow involvement is of unknown prognostic relevance <ref name=":0" />.		SS is aggressive; however, prognosis is variable and largely depends on stage. A median survival of 32 months and a 5-year survival rate of 10-30% has been reported <ref name=":0" />. Death usually results from opportunistic infections, as SS patients are at an increased risk for infection due to underlying immune dysfunction<ref name=":1" />. Lymph node and visceral involvement are poor prognostic factors, as is the degree of peripheral blood involvement by Sézary cells. Bone marrow involvement is of unknown prognostic relevance <ref name=":0" />.

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	Recurrent gain-of-function mutations in SS include ''PLGC1'', ''CD28'', and ''TNFRSF1B''. Recurrent loss-of-function mutations include ''ARID1A'', which has been observed in 40% of SS cases<ref name=":0" />.		Recurrent gain-of-function mutations in SS include ''PLGC1'', ''CD28'', and ''TNFRSF1B''. Recurrent loss-of-function mutations include ''ARID1A'', which has been observed in 40% of SS cases<ref name=":0" />.

	Somatic duplications can be found ranging from duplications of chromosome bands (8p23.3-q24.3, 17p11.2-q23.2) to entire chromosomes (chr 18). Several somatic deletions have also been demonstrated including a 15-25 Mb deletion on 17p12-p13.3<ref name=":2" />.		Somatic duplications can be found ranging from duplications of chromosome bands (8p23.3-q24.3, 17p11.2-q23.2) to entire chromosomes (chr 18). Several somatic deletions have also been demonstrated including a 15-25 Mb deletion on 17p12-p13.3<ref name=":1" />.
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	Numerical and structural alterations are common in SS. These include loss of 1p, 6q, and 10q with gains of 7 and 8q<ref name=":4">{{Cite journal\|displayauthors=1\|last=Almeida\|first=Ana\|date=December 2015\|title=The mutational landscape of cutaneous T cell lymphoma and Sezary syndrome\|url=\|journal=Nature Genetics\|volume=47\|pages=\|via=}}</ref><ref name=":0" />. Isochromosome 17q is a recurrent finding in SS<ref name=":0" />.		Numerical and structural alterations are common in SS. These include loss of 1p, 6q, and 10q with gains of 7 and 8q<ref name=":1" /><ref name=":4">{{Cite journal\|displayauthors=1\|last=Almeida\|first=Ana\|date=December 2015\|title=The mutational landscape of cutaneous T cell lymphoma and Sezary syndrome\|url=\|journal=Nature Genetics\|volume=47\|pages=\|via=}}</ref><ref name=":2">{{Cite journal\|last=da Silva Almeida\|first=Ana Carolina\|last2=Abate\|first2=Francesco\|last3=Khiabanian\|first3=Hossein\|last4=Martinez-Escala\|first4=Estela\|last5=Guitart\|first5=Joan\|last6=Tensen\|first6=Cornelis P.\|last7=Vermeer\|first7=Maarten H.\|last8=Rabadan\|first8=Raul\|last9=Ferrando\|first9=Adolfo\|date=2015-12\|title=The mutational landscape of cutaneous T cell lymphoma and Sézary syndrome\|url=https://pubmed.ncbi.nlm.nih.gov/26551667\|journal=Nature Genetics\|volume=47\|issue=12\|pages=1465–1470\|doi=10.1038/ng.3442\|issn=1546-1718\|pmc=4878831\|pmid=26551667}}</ref>. Isochromosome 17q is a recurrent finding in SS<ref name=":0" />.

	Deletions are often associated with loss of tumor suppressor genes such as recurrent deletions involving 17p13.1 (TP53), 13q14.2 (RB1), 10q23.3 (PTEN) and 12p13.1 (CDKN1B). Focal chromosome 2p23.3 deletions (DNMT3A) were observed.<ref name=":4" />		Deletions are often associated with loss of tumor suppressor genes such as recurrent deletions involving 17p13.1 (TP53), 13q14.2 (RB1), 10q23.3 (PTEN) and 12p13.1 (CDKN1B). Focal chromosome 2p23.3 deletions (DNMT3A) were observed<ref name=":2" />.

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	<blockquote class="blockedit">{{Box-round\|title=v4:Gene Mutations (SNV/INDEL)\|The content below was from the old template. Please incorporate above.}}</blockquote>		<blockquote class="blockedit">{{Box-round\|title=v4:Gene Mutations (SNV/INDEL)\|The content below was from the old template. Please incorporate above.}}</blockquote>

	The mutational landscape of Sezary syndrome is complex and over 1000 different gene mutations have been identified. Mutational signature characterized by C>T substitutions at NpCpG trinucleotides and C>A substitutions at CpCpN trinucleotides and C>T substitutions at CpCpN and TpCpN trinulceotides have been identified<ref name=":4" />.		The mutational landscape of Sezary syndrome is complex and over 1000 different gene mutations have been identified. Mutational signature characterized by C>T substitutions at NpCpG trinucleotides and C>A substitutions at CpCpN trinucleotides and C>T substitutions at CpCpN and TpCpN trinulceotides have been identified<ref name=":2" />.

	''RHOA'' mutations have also been described in SS. Mutations (including single nucleotide mutations and copy number variants) in the JAK/STAT pathway likely result in the constitutive activation of ''STAT3'' in Sézary cells. Inactivating mutations in ''TP53'' and deletions of ''CDKN2A'' (p16INK4a) are frequent. Mutations in ''DNMT3A'' have been reported in SS<ref name=":0" />.		''RHOA'' mutations have also been described in SS. Mutations (including single nucleotide mutations and copy number variants) in the JAK/STAT pathway likely result in the constitutive activation of ''STAT3'' in Sézary cells. Inactivating mutations in ''TP53'' and deletions of ''CDKN2A'' (p16INK4a) are frequent. Mutations in ''DNMT3A'' have been reported in SS<ref name=":0" />.

	Mutations in epigenetic regulator genes including TET2, CREBPP, KMT2C (MLL3) histone H3 lysine 4 (H3K4) methyltransferase, WI/SNF, and NuRD chromatin-remodeling complexes have been demonstrated as well<ref name=":4" />.		Mutations in epigenetic regulator genes including TET2, CREBPP, KMT2C (MLL3) histone H3 lysine 4 (H3K4) methyltransferase, WI/SNF, and NuRD chromatin-remodeling complexes have been demonstrated as well<ref name=":2" />.

	Recurrent mutations in TP53, ITPR1, DSC1 and PKHD1L1 are found in a cohort study by Prasad et al. The study found damaging mutations to ITPR1 in two Sezary Syndrome patients. ITPR1 mediates calcium release from the endoplasmic reticulum and may be functional partners with BCL2, which is an apoptosis suppressor.		Recurrent mutations in TP53, ITPR1, DSC1 and PKHD1L1 are found in a cohort study by Prasad et al. The study found damaging mutations to ITPR1 in two Sezary Syndrome patients. ITPR1 mediates calcium release from the endoplasmic reticulum and may be functional partners with BCL2, which is an apoptosis suppressor.

	Mutations in the p53, p15, p16, JunB, and PTEN genes are generally found in late-stage disease, suggesting that they are secondary genetic events after disease initiation<ref name=":3">{{Cite journal~~\|displayauthors=1~~\|last=Hwang\|first=Sam\|date=~~March~~ 15~~, 2008~~\|title=Mycosis ~~fungicides~~ and ~~Sezary~~ syndrome\|url=\|journal=Lancet\|volume=371\|pages=\|~~via~~=}}</ref>.		Mutations in the p53, p15, p16, JunB, and PTEN genes are generally found in late-stage disease, suggesting that they are secondary genetic events after disease initiation<ref name=":3">{{Cite journal\|last=Hwang\|first=Sam T.\|last2=Janik\|first2=John E.\|last3=Jaffe\|first3=Elaine S.\|last4=Wilson\|first4=Wyndham H.\|date=2008-03-15\|title=Mycosis fungoides and Sézary syndrome\|url=https://pubmed.ncbi.nlm.nih.gov/18342689\|journal=Lancet (London, England)\|volume=371\|issue=9616\|pages=945–957\|doi=10.1016/S0140-6736(08)60420-1\|issn=1474-547X\|pmid=18342689}}</ref>.

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	Loss of Fas expression, which is involved in T-cell apoptotic pathways, has also been reported. Specifically, changes affecting the Fas ligand is seen in 50-83% of cases. Loss of Fas expression is seen in 14-59% of cases<ref name=":3" />.		Loss of Fas expression, which is involved in T-cell apoptotic pathways, has also been reported. Specifically, changes affecting the Fas ligand is seen in 50-83% of cases. Loss of Fas expression is seen in 14-59% of cases<ref name=":3" />.

	Genes involved in NF-kB signaling, chromatin remodeling, and DNA damage response have also been found to be altered. Notably, alterations to signaling pathways including Jak/signal transducer and activator of transcription (STAT) signaling and cell-cycle checkpoint have been shown to be involved in the pathogenesis<ref name=":2" />.<br />		Genes involved in NF-kB signaling, chromatin remodeling, and DNA damage response have also been found to be altered. Notably, alterations to signaling pathways including Jak/signal transducer and activator of transcription (STAT) signaling and cell-cycle checkpoint have been shown to be involved in the pathogenesis<ref name=":1" />.<br />

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	==References==		==References==
	1. Arber DA, et al., (2017). Sézary syndrome, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p390-391.

	~~2. Prasad et al. Identification of Gene Mutations and Fusion Genes in Patients with Sezary Syndrome. Journal of Investigative Dermatology (2016), volume 136.~~

	~~3. Hwang ST, Janik JE, Jaffe ES, Wilson WH, (2008). Mycosis fungoides and Sezary syndrome, in Lancet. Vol 371, March 15 2008.~~

	~~4. Rook, AH and Olsen, EA. Clinical presentation, pathologic features, and Diagnosis of Sézary syndrome. UpToDate. Uptodate.com. Last updated: June 24, 2020. Date accessed: January 29, 2021.~~

	~~5. Almeida et al. The mutational landscape of cutaneous T cell lymphoma and Sezary Syndrome. Nature genetics. Volume 47. Number 12. December 2015.~~

	~~<br />~~


	<references />		<references />

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2025-02-11T21:54:19Z

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Bailey.Glen at 19:00, 10 February 2025

2025-02-10T19:00:24Z

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Bailey.Glen at 18:32, 10 February 2025

2025-02-10T18:32:23Z

← Older revision		Revision as of 13:32, 10 February 2025
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	<blockquote class='blockedit'>{{Box-round\|title=v4:Clinical Features\|The content below was from the old template. Please incorporate above.}}		<blockquote class='blockedit'>{{Box-round\|title=v4:Clinical Features\|The content below was from the old template. Please incorporate above.}}</blockquote>

	Erythroderma and generalized lymphadenopathy developing over weeks to months. Scaling is commonly found on the patch and plaque lesions. The lesions are usually located in areas infrequently exposed to sunlight<ref name=":3" />. Pruritis is the most commonly reported symptom<ref name=":1" />. Other features include alopecia, ectropion, palmar or plantar hyperkeratosis, and onychodystrophy.		Erythroderma and generalized lymphadenopathy developing over weeks to months. Scaling is commonly found on the patch and plaque lesions. The lesions are usually located in areas infrequently exposed to sunlight<ref name=":3" />. Pruritis is the most commonly reported symptom<ref name=":1" />. Other features include alopecia, ectropion, palmar or plantar hyperkeratosis, and onychodystrophy.
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	An increased prevalence of secondary cutaneous and systemic malignancies has been reported in SS, likely a result of the hypogammaglobulinemia associated with the skewed T-cell ratio and loss of normal circulating CD4+ T-cells <ref name=":0" />.		An increased prevalence of secondary cutaneous and systemic malignancies has been reported in SS, likely a result of the hypogammaglobulinemia associated with the skewed T-cell ratio and loss of normal circulating CD4+ T-cells <ref name=":0" />.

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	==Sites of Involvement==		==Sites of Involvement==
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	Clonal T cell receptor gene (TCR) rearrangement is characteristic of SS. Characteristically, ''PLS3'', ''DNM3'', ''TWIST1'', and ''EPHA4'' are overexpressed, and ''STAT4'' is underexpressed.		Clonal T cell receptor gene (TCR) rearrangement is characteristic of SS. Characteristically, ''PLS3'', ''DNM3'', ''TWIST1'', and ''EPHA4'' are overexpressed, and ''STAT4'' is underexpressed.
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	Gene fusion between CTLA4 and CD28 is highly expressed. Additional fusion events include TYK2-UPF1, COL25A1-NFKB2, FASN-SGMS1, SMS1-ZEB1, SPATA21-RASA2, PITRM1-HK1, and BCR-NDUFAF6<ref name=":2" />.		Gene fusion between CTLA4 and CD28 is highly expressed. Additional fusion events include TYK2-UPF1, COL25A1-NFKB2, FASN-SGMS1, SMS1-ZEB1, SPATA21-RASA2, PITRM1-HK1, and BCR-NDUFAF6<ref name=":2" />.

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	* Individual Region Genomic Gain/Loss/LOH		* Individual Region Genomic Gain/Loss/LOH
	* Characteristic Chromosomal Patterns		* Characteristic Chromosomal Patterns
	* Gene Mutations (SNV/INDEL)}}		* Gene Mutations (SNV/INDEL)}}</blockquote>

	SS is aggressive; however, prognosis is variable and largely depends on stage. A median survival of 32 months and a 5-year survival rate of 10-30% has been reported <ref name=":0" />. Death usually results from opportunistic infections, as SS patients are at an increased risk for infection due to underlying immune dysfunction<ref name=":1" />. Lymph node and visceral involvement are poor prognostic factors, as is the degree of peripheral blood involvement by Sézary cells. Bone marrow involvement is of unknown prognostic relevance <ref name=":0" />.		SS is aggressive; however, prognosis is variable and largely depends on stage. A median survival of 32 months and a 5-year survival rate of 10-30% has been reported <ref name=":0" />. Death usually results from opportunistic infections, as SS patients are at an increased risk for infection due to underlying immune dysfunction<ref name=":1" />. Lymph node and visceral involvement are poor prognostic factors, as is the degree of peripheral blood involvement by Sézary cells. Bone marrow involvement is of unknown prognostic relevance <ref name=":0" />.

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	==Individual Region Genomic Gain / Loss / LOH==		==Individual Region Genomic Gain / Loss / LOH==
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	Recurrent gain-of-function mutations in SS include ''PLGC1'', ''CD28'', and ''TNFRSF1B''. Recurrent loss-of-function mutations include ''ARID1A'', which has been observed in 40% of SS cases<ref name=":0" />.		Recurrent gain-of-function mutations in SS include ''PLGC1'', ''CD28'', and ''TNFRSF1B''. Recurrent loss-of-function mutations include ''ARID1A'', which has been observed in 40% of SS cases<ref name=":0" />.

	Somatic duplications can be found ranging from duplications of chromosome bands (8p23.3-q24.3, 17p11.2-q23.2) to entire chromosomes (chr 18). Several somatic deletions have also been demonstrated including a 15-25 Mb deletion on 17p12-p13.3<ref name=":2" />.		Somatic duplications can be found ranging from duplications of chromosome bands (8p23.3-q24.3, 17p11.2-q23.2) to entire chromosomes (chr 18). Several somatic deletions have also been demonstrated including a 15-25 Mb deletion on 17p12-p13.3<ref name=":2" />.
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	==Characteristic Chromosomal Patterns==		==Characteristic Chromosomal Patterns==
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	Numerical and structural alterations are common in SS. These include loss of 1p, 6q, and 10q with gains of 7 and 8q<ref name=":4">{{Cite journal\|displayauthors=1\|last=Almeida\|first=Ana\|date=December 2015\|title=The mutational landscape of cutaneous T cell lymphoma and Sezary syndrome\|url=\|journal=Nature Genetics\|volume=47\|pages=\|via=}}</ref><ref name=":0" />. Isochromosome 17q is a recurrent finding in SS<ref name=":0" />.		Numerical and structural alterations are common in SS. These include loss of 1p, 6q, and 10q with gains of 7 and 8q<ref name=":4">{{Cite journal\|displayauthors=1\|last=Almeida\|first=Ana\|date=December 2015\|title=The mutational landscape of cutaneous T cell lymphoma and Sezary syndrome\|url=\|journal=Nature Genetics\|volume=47\|pages=\|via=}}</ref><ref name=":0" />. Isochromosome 17q is a recurrent finding in SS<ref name=":0" />.
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	Deletions are often associated with loss of tumor suppressor genes such as recurrent deletions involving 17p13.1 (TP53), 13q14.2 (RB1), 10q23.3 (PTEN) and 12p13.1 (CDKN1B). Focal chromosome 2p23.3 deletions (DNMT3A) were observed.<ref name=":4" />		Deletions are often associated with loss of tumor suppressor genes such as recurrent deletions involving 17p13.1 (TP53), 13q14.2 (RB1), 10q23.3 (PTEN) and 12p13.1 (CDKN1B). Focal chromosome 2p23.3 deletions (DNMT3A) were observed.<ref name=":4" />

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	==Gene Mutations (SNV / INDEL)==		==Gene Mutations (SNV / INDEL)==
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	The mutational landscape of Sezary syndrome is complex and over 1000 different gene mutations have been identified. Mutational signature characterized by C>T substitutions at NpCpG trinucleotides and C>A substitutions at CpCpN trinucleotides and C>T substitutions at CpCpN and TpCpN trinulceotides have been identified<ref name=":4" />.		The mutational landscape of Sezary syndrome is complex and over 1000 different gene mutations have been identified. Mutational signature characterized by C>T substitutions at NpCpG trinucleotides and C>A substitutions at CpCpN trinucleotides and C>T substitutions at CpCpN and TpCpN trinulceotides have been identified<ref name=":4" />.
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	Mutations in the p53, p15, p16, JunB, and PTEN genes are generally found in late-stage disease, suggesting that they are secondary genetic events after disease initiation<ref name=":3" />.		Mutations in the p53, p15, p16, JunB, and PTEN genes are generally found in late-stage disease, suggesting that they are secondary genetic events after disease initiation<ref name=":3" />.

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	==Epigenomic Alterations==		==Epigenomic Alterations==
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	Loss of Fas expression, which is involved in T-cell apoptotic pathways, has also been reported. Specifically, changes affecting the Fas ligand is seen in 50-83% of cases. Loss of Fas expression is seen in 14-59% of cases<ref name=":3" />.		Loss of Fas expression, which is involved in T-cell apoptotic pathways, has also been reported. Specifically, changes affecting the Fas ligand is seen in 50-83% of cases. Loss of Fas expression is seen in 14-59% of cases<ref name=":3" />.
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	Genes involved in NF-kB signaling, chromatin remodeling, and DNA damage response have also been found to be altered. Notably, alterations to signaling pathways including Jak/signal transducer and activator of transcription (STAT) signaling and cell-cycle checkpoint have been shown to be involved in the pathogenesis<ref name=":2" />.<br />		Genes involved in NF-kB signaling, chromatin remodeling, and DNA damage response have also been found to be altered. Notably, alterations to signaling pathways including Jak/signal transducer and activator of transcription (STAT) signaling and cell-cycle checkpoint have been shown to be involved in the pathogenesis<ref name=":2" />.<br />

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	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==

Bailey.Glen at 22:35, 6 September 2024

2024-09-06T22:35:52Z

← Older revision		Revision as of 17:35, 6 September 2024
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	__TOC__		__TOC__

	==~~Cancer Category / Type~~==		==WHO Classification of Disease==

	Mature T-cell ~~neoplasm / Cutaneous~~ T-cell ~~lymphoma~~		{\| class="wikitable"
			!Structure
	~~==Cancer Sub-Classification /~~ Subtype==		!Disease
			\|-
	~~Sézary syndrome~~		\|Book
			\|Haematolymphoid Tumours (5th ed.)
			\|-
			\|Category
			\|T-cell and NK-cell lymphoid proliferations and lymphomas
			\|-
			\|Family
			\|Mature T-cell and NK-cell neoplasms
			\|-
			\|Type
			\|Mature T-cell and NK-cell leukaemias
			\|-
			\|Subtype(s)
			\|Sezary syndrome
			\|}

	==Definition / Description of Disease==		==Definition / Description of Disease==

Bailey.Glen at 22:11, 6 September 2024

2024-09-06T22:11:01Z

Show changes