Difference between revisions of "Anaplastic Large Cell Lymphoma, ALK-Negative"

From Compendium of Cancer Genome Aberrations
Jump to: navigation, search
(Other Mutations)
(Genomic Gain/Loss/LOH)
Line 75: Line 75:
 
==Genomic Gain/Loss/LOH==
 
==Genomic Gain/Loss/LOH==
  
Put your text here and/or fill in the table
+
* In general, recurrent lesions are more common in Alk- than Alk+ disease
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Chromosome Number!!Gain/Loss/Amp/LOH!!Region
 
!Chromosome Number!!Gain/Loss/Amp/LOH!!Region
 +
!Genes
 +
!Prevalence
 
|-
 
|-
 
|1q||Gain||
 
|1q||Gain||
 +
|numerous
 +
|
 
|-
 
|-
 
|6p
 
|6p
 
|Gain
 
|Gain
 +
|
 +
|
 
|
 
|
 
|-
 
|-
|8q||Gain||24.22  
+
|8q||Gain||24.22
 +
|NDRG1, PHF20L1, SLA, ST3GAL1, TG, WISP1
 +
|23%
 
|-
 
|-
 
|12q
 
|12q
 
|Gain
 
|Gain
 +
|
 +
|
 
|
 
|
 
|-
 
|-
|4q
+
|6q
 
|Loss
 
|Loss
 +
|21
 
|
 
|
 +
|56%
 
|-
 
|-
|16q
+
|13q
 
|Loss
 
|Loss
|23.2
+
|32.3-q33.3
 +
|
 +
|23%
 
|-
 
|-
|13q
+
|16q
 
|Loss
 
|Loss
|32.3-q33.3
+
|23.2
 +
|MAF, WWOX
 +
|29%
 
|-
 
|-
 
|17p
 
|17p
 
|Loss
 
|Loss
|13.3-p12  
+
|13.3-p12
|}
+
|TP53
 
+
|42%
{| class="wikitable"
 
!Lesion/Cytoband
 
!Start*
 
!Size, kb*
 
!RefSeq genes†
 
!ALCL %
 
!ALK<sup>−</sup>ALCL %
 
!ALK<sup>+</sup>ALCL %
 
!''P''
 
|-
 
|'''Losses'''
 
|
 
|
 
|
 
|
 
|
 
|
 
|
 
|-
 
| 17p13.3-p12
 
|526
 
|11 747.22
 
|>20 (TP53)
 
|25
 
|42  
 
|9
 
|.002
 
|-
 
| 6q21
 
|105 944 900
 
|951.75
 
|''ATG5'', ''PRDM1''
 
|19
 
|56
 
|6
 
|<.001
 
|-
 
| 13q32.3-q33.3
 
|99 090 837
 
|9349.42
 
|>20
 
|16
 
|23
 
|9
 
|ns
 
|-
 
| 16q23.2
 
|78 371 498
 
|11 642
 
|''MAF'', ''WWOX''
 
|16
 
|29
 
|3
 
|.004
 
|-
 
|'''Gains'''
 
|
 
|
 
|
 
|
 
|
 
|
 
|
 
|-
 
| 1q
 
|121 344 093
 
|127 880.29
 
|>20
 
|23
 
|32
 
|15
 
|ns
 
|-
 
| 8q24.22
 
|133 799 280
 
|919.4
 
|''NDRG1'', ''PHF20L1'', ''SLA'', ''ST3GAL1'', ''TG'', ''WISP1''
 
|17
 
|23
 
|12
 
|ns
 
 
|}
 
|}
  
 
==Gene Mutations (SNV/INDEL)==
 
==Gene Mutations (SNV/INDEL)==
 
{| class="wikitable sortable"
 
|-
 
!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
 
|-
 
|PRDM1
 
|
 
|Transcriptional Repressor
 
|LOF
 
|56%
 
|-
 
|TP53|| ||Tumor Suppressor||EXAMPLE LOF||42%
 
|}
 
 
 
===Other Mutations===
 
===Other Mutations===
  
* PRDM1
+
*TET2
* TP53
+
*FAS
* TET2
+
*STIM2
* FAS
 
* STIM2
 
 
 
{| class="wikitable sortable"
 
|-
 
!Type!!Gene/Region/Other
 
|-
 
|Concomitant Mutations||EXAMPLE IDH1 R123H
 
|-
 
|Secondary Mutations||EXAMPLE Trisomy 7
 
|-
 
|Mutually Exclusive||EXAMPLE EGFR Amplification
 
|}
 
  
 
==Epigenomics (Methylation)==
 
==Epigenomics (Methylation)==

Revision as of 18:07, 28 July 2020

This page is under construction
We need your help!
Please consider joining in the project and submitting a review

Primary Author(s)*

Derick Okwan-Duodu, MD, PhD; Sumire Kitahara, MD

Cancer Category/Type

Mature T-cell neoplasm

Cancer Sub-Classification / Subtype

Definition / Description of Disease

This entity of anaplastic large cell lymphoma is morphologically and phenotypically indistinguishable from Alk-Positive anaplastic large cell lymphoma.

Synonyms / Terminology

  • N/A

Epidemiology / Prevalence

  • More common in adults than children
  • Less than 3% of all Non-Hodgkin's lymphoma
  • M:F 1.5:1

Clinical Features

  • B symptoms of weight loss, fevers, chills
  • Peripheral and/or abdominal lymphadenopathy
  • Most patients present with advanced stage disease

Sites of Involvement

  • Nodal (predominantly abdominal lymphadenopathy
  • Extranodal (skin, bone, gastrointestinal)

Morphologic Features

  • Tissue effacement by cohesive sheets of large, pleomorphic neoplastic cells
  • Prominent nucleoli
  • Hallmark cells
  • High nuclear-cytoplasmic ratio
  • Eosinophils common

Immunophenotype

Finding Marker
Positive (universal) strong CD30, CD43 (almost universally)
Positive (subset) CD2, CD3, CD4, CD5, TIA1, granzyme B, perforin
Negative (universal) ALK, EBER, LMP-1
Negative (DUSP22 rearranged subset) CD2, CD3, CD5, TIA1, granzyme B, perforin

Chromosomal Rearrangements (Gene Fusions)[1][2]

Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Prevalence
t(6;7)(p25.3;q32.3) DUSP22/IRF4 30%[3]
t(3;3)(q22;q26.2) P63/TBL1XR1 8%[3]

Characteristic Chromosomal Aberrations / Patterns

Genomic Gain/Loss/LOH

  • In general, recurrent lesions are more common in Alk- than Alk+ disease
Chromosome Number Gain/Loss/Amp/LOH Region Genes Prevalence
1q Gain numerous
6p Gain
8q Gain 24.22 NDRG1, PHF20L1, SLA, ST3GAL1, TG, WISP1 23%
12q Gain
6q Loss 21 56%
13q Loss 32.3-q33.3 23%
16q Loss 23.2 MAF, WWOX 29%
17p Loss 13.3-p12 TP53 42%

Gene Mutations (SNV/INDEL)

Other Mutations

  • TET2
  • FAS
  • STIM2

Epigenomics (Methylation)

  • N/A

Genes and Main Pathways Involved

JAK-STAT

Diagnostic Testing Methods

ERBB4 and COL29A1 co-expressing subtype[4]

DUSP22- IRF4[5]

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

  • 3-gene model (TNFRSF8, BATF3, and TMOD1) distinguishes Alk- ALCL from PTCL with > 97% accuracy[6]
  • 5 year overall survival > 90% for DUSP22 rearranged Alk- ALCL, 17% for TP63-rearranged Alk- ALCL, and 42% for cases lacking DUSP22, TP63 and ALK[3]

Familial Forms

  • Not described

Other Information

Put your text here

Links

Put your links here (use "Link" icon at top of page)

References

(use "Cite" icon at top of page)

  1. Pileri, Stefano (2011-05-01). "Faculty Opinions recommendation of Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing".
  2. Wisell, J. (2012-01). "Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies". Yearbook of Pathology and Laboratory Medicine. 2012: 83–84. doi:10.1016/j.ypat.2011.11.134. ISSN 1077-9108. Check date values in: |date= (help)
  3. 3.0 3.1 3.2 Er, Parrilla Castellar; et al. (2014). "ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes". doi:10.1182/blood-2014-04-571091. PMC 4148769. PMID 24894770.CS1 maint: PMC format (link)
  4. I, Scarfò; et al. (2016). "Identification of a new subclass of ALK-negative ALCL expressing aberrant levels of ERBB4 transcripts". PMID 26463425.
  5. Al, Feldman; et al. (2011). "Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing". doi:10.1182/blood-2010-08-303305. PMC 3035081. PMID 21030553.CS1 maint: PMC format (link)
  6. "ALK-negative anaplastic large cell lymphoma". Definitions. Qeios. 2020-02-10.

Notes

*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.