Compendium of Cancer Genome Aberrations

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<span style="color:#0070C0">EGFR(''General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples). Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])''</span>
{{DISPLAYTITLE:Phyllodes tumour}}


==Primary Author(s)*==
[[BRST5:Table_of_Contents|Breast Tumours (WHO Classification, 5th ed.)]]


H. Evin Gulbahce, MD, MSCI, University of Utah, UT, USA
{{Under Construction}}


Emilie Lalonde, PhD, London Health Sciences Center and Western University, London, Ontario, Canada
<span style="color:#0070C0">(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)''</span>
 
==Primary Author(s)*==
Patricija Zot, MD, Mayo Clinic, MN, USA
Emilie Lalonde, PhD, London Health Sciences Center and Western University, London, Ontario, Canada  
 
__TOC__
 
==Cancer Category / Type==
 
Breast cancer / Fibroepithelial Tumors of the Breast


==Cancer Sub-Classification / Subtype==
H. Evin Gulbahce, MD, MSCI, University of Utah, UT, USA


Phyllodes Tumor 
Katherine Geiersbach, MD, Mayo Clinic - Rochester, MN, USA


==Definition / Description of Disease==
==WHO Classification of Disease==


Phyllodes Tumor (PT) is a rare fibroepithelial neoplasm. Phyllodes tumors are subclassified as benign, borderline, or malignant based on a combination of several histologic features including stromal cellularity, atypia, mitotic activity, tumor border, and stromal overgrowth. The majority (60-75%) are benign, 15-25% are borderline, 8-20% are malignant.
==Synonyms / Terminology==
Cystosarcoma phyllodes ''(Historical)''
==Epidemiology / Prevalence==
Rare, less than 1% of all breast tumors and 2.5% of all fibroepithelial neoplasms. The incidence is higher, ~7% of breast tumors, among Asian women. Phyllodes tumor is more common in older women (in their 50s), in contrast to fibroadenomas which are more common in younger women (in their 20s).
==Clinical Features==
PT usually present clinically as unilateral, well circumscribed mass. Lymph node metastases are infrequent.
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
!Structure
|
!Disease
|-
|-
|'''Laboratory Findings'''
|Book
|
|Breast Tumours (5th ed.)
|}
 
==Sites of Involvement==
 
There is no specific predilection for location in the breast.
 
==Morphologic Features==
 
''Malignant'' phyllodes tumor is diagnosed when all of the following morphologic features are present <ref>{{Cite journal|last=Zhang|first=Yanhong|last2=Kleer|first2=Celina G.|date=2016-07|title=Phyllodes Tumor of the Breast: Histopathologic Features, Differential Diagnosis, and Molecular/Genetic Updates|url=https://pubmed.ncbi.nlm.nih.gov/27362571|journal=Archives of Pathology & Laboratory Medicine|volume=140|issue=7|pages=665–671|doi=10.5858/arpa.2016-0042-RA|issn=1543-2165|pmid=27362571}}</ref>:
 
·       Marked stromal nuclear pleomorphism
 
·       Stromal overgrowth (absence of epithelial elements in one low-power microscopic field)
 
·       Increased mitoses (>=10 mitoses/10 high power fields (hpf))
 
·       Increased stromal cellularity
 
·       Permeative tumor border
 
Or, when malignant heterologous elements are present (with the exception of well-differentiated liposarcoma).
 
''Borderline'' phyllodes tumor is diagnosed when one or more of the above adverse histologic features are present but histologic criteria fall short of malignant PT.
 
''Benign'' phyllodes tumor has well defined borders, shows mild stromal cellularity, does not show atypia, and has a mitotic count <5/10 hpf
 
==Immunophenotype==
 
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
|Category
|Fibroepithelial tumours and hamartomas of the breast
|-
|-
|Positive (universal)||CD34 (in benign PT)
|Family
|Fibroepithelial tumours and hamartomas of the breast: Introduction
|-
|-
|Positive (subset)||EGFR (97%) of Malignant PT <ref>{{Cite journal|last=Gatalica|first=Zoran|last2=Vranic|first2=Semir|last3=Ghazalpour|first3=Anatole|last4=Xiu|first4=Joanne|last5=Ocal|first5=Idris Tolgay|last6=McGill|first6=John|last7=Bender|first7=Ryan P.|last8=Discianno|first8=Erin|last9=Schlum|first9=Aaron|date=2016-01-12|title=Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast|url=https://pubmed.ncbi.nlm.nih.gov/26625196|journal=Oncotarget|volume=7|issue=2|pages=1707–1716|doi=10.18632/oncotarget.6421|issn=1949-2553|pmc=4811491|pmid=26625196}}</ref>, CD34 (majority of borderline PT, subset of malignant PT), beta-catenin (94%) of benign lesions
|Type
|Phyllodes tumour
|-
|-
|Negative (universal)||p63 and p40 (in benign and borderline PT)
|Subtype(s)
|N/A
|}
 
==Related Terminology==
 
{| class="wikitable"
|+
|Acceptable
|N/A
|-
|-
|Negative (subset)||EXAMPLE CD4
|Not Recommended
|Cystosarcoma phyllodes
|}
|}


==Chromosomal Rearrangements (Gene Fusions)==
==Gene Rearrangements==


<br />
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
!Diagnostic Significance (Yes, No or Unknown)
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Prognostic Significance (Yes, No or Unknown)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Therapeutic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Notes
!Clinical Relevance Details/Other Notes
|-
|''EGFR''
|N/A
|Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
|N/A
|Recurrent
|D, P, T
|
|
|-
|-
|NA|| || ||
|
|
|
|
|
|
|
|
|}
==Individual Region Genomic Gain / Loss / LOH==
{| class="wikitable sortable"
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|''EGFR''
|Amplification
|
|
|7p11.2
|No
|No
|No
|Borderline and malignant tumors <ref name=":0">{{Cite journal|last=Tan|first=Jing|last2=Ong|first2=Choon Kiat|last3=Lim|first3=Weng Khong|last4=Ng|first4=Cedric Chuan Young|last5=Thike|first5=Aye Aye|last6=Ng|first6=Ley Moy|last7=Rajasegaran|first7=Vikneswari|last8=Myint|first8=Swe Swe|last9=Nagarajan|first9=Sanjanaa|date=2015-11|title=Genomic landscapes of breast fibroepithelial tumors|url=https://pubmed.ncbi.nlm.nih.gov/26437033|journal=Nature Genetics|volume=47|issue=11|pages=1341–1345|doi=10.1038/ng.3409|issn=1546-1718|pmid=26437033}}</ref> <ref>{{Cite journal|last=Gatalica|first=Zoran|last2=Vranic|first2=Semir|last3=Ghazalpour|first3=Anatole|last4=Xiu|first4=Joanne|last5=Ocal|first5=Idris Tolgay|last6=McGill|first6=John|last7=Bender|first7=Ryan P.|last8=Discianno|first8=Erin|last9=Schlum|first9=Aaron|date=2016-01-12|title=Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast|url=https://pubmed.ncbi.nlm.nih.gov/26625196|journal=Oncotarget|volume=7|issue=2|pages=1707–1716|doi=10.18632/oncotarget.6421|issn=1949-2553|pmc=4811491|pmid=26625196}}</ref>
|-
|''RB1''
|Deletion
|
|
|13q14.2
|No
|No
|No
|Mostly borderline or malignant tumors <ref name=":1">{{Cite journal|last=Kim|first=Ji-Yeon|last2=Yu|first2=Jong Han|last3=Nam|first3=Seok Jin|last4=Kim|first4=Seok Won|last5=Lee|first5=Se Kyung|last6=Park|first6=Woong-Yang|last7=Noh|first7=Dong-Young|last8=Nam|first8=Do-Hyun|last9=Park|first9=Yeon Hee|date=2018-02|title=Genetic and Clinical Characteristics of Phyllodes Tumors of the Breast|url=https://pubmed.ncbi.nlm.nih.gov/29145046|journal=Translational Oncology|volume=11|issue=1|pages=18–23|doi=10.1016/j.tranon.2017.10.002|issn=1936-5233|pmc=5684533|pmid=29145046}}</ref><ref name=":0" /><ref name=":2">{{Cite journal|last=Tsang|first=Julia Y.|last2=Shao|first2=Yan|last3=Poon|first3=Ivan K.|last4=Ni|first4=Yun-Bi|last5=Kwan|first5=Johnny S.|last6=Chow|first6=Chit|last7=Shea|first7=Ka-Ho|last8=Tse|first8=Gary M.|date=2022-10|title=Analysis of recurrent molecular alterations in phyllodes tumour of breast: insights into prognosis and pathogenesis|url=https://pubmed.ncbi.nlm.nih.gov/35691725|journal=Pathology|volume=54|issue=6|pages=678–685|doi=10.1016/j.pathol.2022.03.008|issn=1465-3931|pmid=35691725}}</ref>
|-
|''PTEN''
|Deletion
|
|
|10q23.31
|No
|Yes
|No
|Malignant tumors; less common <ref name=":1" /><ref name=":2" />
|-
|''CDKN2A''/ ''CDKN2B''
|Deletion
|
|
|9p21.3
|No
|Yes
|No
|Borderline and malignant tumors; associated with recurrent disease <ref name=":2" />
|}
|}
==Characteristic Chromosomal Patterns==


Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>
{| class="wikitable sortable"
|-
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE
Co-deletion of 1p and 18q
|Yes
|No
|No
|EXAMPLE:
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|}
==Gene Mutations (SNV / INDEL)==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span>


==Individual Region Genomic Gain/Loss/LOH==
<br />
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!'''Diagnostic Significance (Yes, No or Unknown)'''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Prognostic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Therapeutic Significance (Yes, No or Unknown)
!Clinical Relevance Details/Other Notes
!Notes
|-
|-
|MED12
|1
|Gain of function; G44 residue is a hotspot
|Gain
|73%, 67% (PMID:25593300, 26437033)  
|1q (whole arm)
|Often co-occurring RARA, TERT promoter, SETD2, EGFR mutations
|
|Yes
|No
|Unknown
|All (Benign, borderline, and malignant) grades
<br />
|-
|TERT promoter
|
|
|
|
|
|
|Frequency in benign tumors varies, up to 33% across studies<ref name=":0">{{Cite journal|last=Laé|first=Marick|last2=La Rosa|first2=Philippe|last3=Mandel|first3=Jonas|last4=Reyal|first4=Fabien|last5=Hupé|first5=Philippe|last6=Terrier|first6=Philippe|last7=Couturier|first7=Jérôme|date=2016-12|title=Whole-genome profiling helps to classify phyllodes tumours of the breast|url=https://pubmed.ncbi.nlm.nih.gov/27207013|journal=Journal of Clinical Pathology|volume=69|issue=12|pages=1081–1087|doi=10.1136/jclinpath-2016-203684|issn=1472-4146|pmid=27207013}}</ref><ref name=":1">{{Cite journal|last=Jones|first=A. M.|last2=Mitter|first2=R.|last3=Springall|first3=R.|last4=Graham|first4=T.|last5=Winter|first5=E.|last6=Gillett|first6=C.|last7=Hanby|first7=A. M.|last8=Tomlinson|first8=I. P. M.|last9=Sawyer|first9=E. J.|date=2008-04|title=A comprehensive genetic profile of phyllodes tumours of the breast detects important mutations, intra-tumoral genetic heterogeneity and new genetic changes on recurrence|url=https://pubmed.ncbi.nlm.nih.gov/18288784|journal=The Journal of Pathology|volume=214|issue=5|pages=533–544|doi=10.1002/path.2320|issn=0022-3417|pmid=18288784}}</ref><ref name=":2">{{Cite journal|last=Lv|first=Shuhua|last2=Niu|first2=Yun|last3=Wei|first3=Li|last4=Liu|first4=Qingjie|last5=Wang|first5=Xiaowei|last6=Chen|first6=Yan|date=2008-12|title=Chromosomal aberrations and genetic relations in benign, borderline and malignant phyllodes tumors of the breast: a comparative genomic hybridization study|url=https://pubmed.ncbi.nlm.nih.gov/18189161|journal=Breast Cancer Research and Treatment|volume=112|issue=3|pages=411–418|doi=10.1007/s10549-007-9876-1|issn=1573-7217|pmid=18189161}}</ref>
|-
|7
|Amp
|7p11.2
|''EGFR''
|
|
|
|
|Amplification and/or rearrangement (most commonly loss of exons 2-7) in 33% of borderline and malignant tumors<ref name=":3">{{Cite journal|last=Gatalica|first=Zoran|last2=Vranic|first2=Semir|last3=Ghazalpour|first3=Anatole|last4=Xiu|first4=Joanne|last5=Ocal|first5=Idris Tolgay|last6=McGill|first6=John|last7=Bender|first7=Ryan P.|last8=Discianno|first8=Erin|last9=Schlum|first9=Aaron|date=2016-01-12|title=Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast|url=https://pubmed.ncbi.nlm.nih.gov/26625196|journal=Oncotarget|volume=7|issue=2|pages=1707–1716|doi=10.18632/oncotarget.6421|issn=1949-2553|pmc=4811491|pmid=26625196}}</ref>
|-
|7
|Gain
|7q
|
|
|
|
|
|
|Observed in 39-57% of malignant tumors, 7-13% of borderline tumors; not observed in benign tumors<ref name=":1" />
|-
|-
|RARA
|8
|
|Gain
|8q
|
|
|
|
|
|
|Significantly more common in malignant vs. borderline tumors<ref name=":0" /><ref name=":1" />
|-
|9
|Loss
|9p21
|''CDKN2A'', ''CDKN2B''
|P
|
|
|Borderline and malignant tumors; associated with recurrence<ref name=":4">{{Cite journal|last=Tsang|first=Julia Y.|last2=Shao|first2=Yan|last3=Poon|first3=Ivan K.|last4=Ni|first4=Yun-Bi|last5=Kwan|first5=Johnny S.|last6=Chow|first6=Chit|last7=Shea|first7=Ka-Ho|last8=Tse|first8=Gary M.|date=2022-10|title=Analysis of recurrent molecular alterations in phyllodes tumour of breast: insights into prognosis and pathogenesis|url=https://pubmed.ncbi.nlm.nih.gov/35691725|journal=Pathology|volume=54|issue=6|pages=678–685|doi=10.1016/j.pathol.2022.03.008|issn=1465-3931|pmid=35691725}}</ref>
|-
|10
|Loss
|10q23.31
|''PTEN''
|P
|
|
|Mostly borderline and malignant tumors<ref>{{Cite journal|last=Kim|first=Ji-Yeon|last2=Yu|first2=Jong Han|last3=Nam|first3=Seok Jin|last4=Kim|first4=Seok Won|last5=Lee|first5=Se Kyung|last6=Park|first6=Woong-Yang|last7=Noh|first7=Dong-Young|last8=Nam|first8=Do-Hyun|last9=Park|first9=Yeon Hee|date=2018-02|title=Genetic and Clinical Characteristics of Phyllodes Tumors of the Breast|url=https://pubmed.ncbi.nlm.nih.gov/29145046|journal=Translational Oncology|volume=11|issue=1|pages=18–23|doi=10.1016/j.tranon.2017.10.002|issn=1936-5233|pmc=5684533|pmid=29145046}}</ref><ref>{{Cite journal|last=Nozad|first=Sahar|last2=Sheehan|first2=Christine E.|last3=Gay|first3=Laurie M.|last4=Elvin|first4=Julia A.|last5=Vergilio|first5=Jo-Anne|last6=Suh|first6=James|last7=Ramkissoon|first7=Shakti|last8=Schrock|first8=Alexa B.|last9=Hirshfield|first9=Kim M.|date=2017-04|title=Comprehensive genomic profiling of malignant phyllodes tumors of the breast|url=https://pubmed.ncbi.nlm.nih.gov/28210881|journal=Breast Cancer Research and Treatment|volume=162|issue=3|pages=597–602|doi=10.1007/s10549-017-4156-1|issn=1573-7217|pmid=28210881}}</ref><ref name=":0" /><ref name=":1" />
|-
|13
|Loss
|13q14.2
|''RB1''
|
|
|
|
|Mostly borderline and malignant tumors<ref name=":0" /><ref name=":1" /><ref name=":2" />
|-
|-
|EGFR
|
|
|
|
|
Line 218: Line 150:
|
|
|
|
|}
==Characteristic Chromosomal or Other Global Mutational Patterns==
<br />
{| class="wikitable sortable"
|-
!Chromosomal Pattern
!Molecular Pathogenesis
!Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|TP53
|
|
|
|
|
|
Line 228: Line 171:
|
|
|
|
|}
==Gene Mutations (SNV/INDEL)==
<br />
{| class="wikitable sortable"
|-
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|PIK3CA
|''FLNA''
|
|
|Oncogene
|Common
|
|
|
|
|No significant difference between benign, borderline, and malignant tumors<ref name=":4" /><ref name=":5">{{Cite journal|last=Tan|first=Jing|last2=Ong|first2=Choon Kiat|last3=Lim|first3=Weng Khong|last4=Ng|first4=Cedric Chuan Young|last5=Thike|first5=Aye Aye|last6=Ng|first6=Ley Moy|last7=Rajasegaran|first7=Vikneswari|last8=Myint|first8=Swe Swe|last9=Nagarajan|first9=Sanjanaa|date=2015-11|title=Genomic landscapes of breast fibroepithelial tumors|url=https://pubmed.ncbi.nlm.nih.gov/26437033|journal=Nature Genetics|volume=47|issue=11|pages=1341–1345|doi=10.1038/ng.3409|issn=1546-1718|pmid=26437033}}</ref>
|-
|''MED12''
|G44 residue is a hotspot
|Oncogene
|Common
|D
|
|
|No significant difference between benign, borderline, and malignant tumors. Frequently co-mutated with ''RARA'', ''TERT'' promoter, ''SETD2'', ''EGFR''.<ref>{{Cite journal|last=Cani|first=Andi K.|last2=Hovelson|first2=Daniel H.|last3=McDaniel|first3=Andrew S.|last4=Sadis|first4=Seth|last5=Haller|first5=Michaela J.|last6=Yadati|first6=Venkata|last7=Amin|first7=Anmol M.|last8=Bratley|first8=Jarred|last9=Bandla|first9=Santhoshi|date=2015-04|title=Next-Gen Sequencing Exposes Frequent MED12 Mutations and Actionable Therapeutic Targets in Phyllodes Tumors|url=https://pubmed.ncbi.nlm.nih.gov/25593300|journal=Molecular cancer research: MCR|volume=13|issue=4|pages=613–619|doi=10.1158/1541-7786.MCR-14-0578|issn=1557-3125|pmc=4936398|pmid=25593300}}</ref><ref name=":5" /><ref name=":4" /> ''MED12'' is also frequently mutated in fibroadenoma, a related fibroepthelial tumor.<ref name=":5" />
|-
|''RARA''
|
|
|Oncogene
|Common
|P
|
|
|Frequently co-mutated with ''MED12''<ref name=":4" /><ref name=":6">{{Cite journal|last=Yeong|first=Joe|last2=Thike|first2=Aye Aye|last3=Young Ng|first3=Cedric Chuan|last4=Md Nasir|first4=Nur Diyana|last5=Loh|first5=Kiley|last6=Teh|first6=Bin Tean|last7=Tan|first7=Puay Hoon|date=2017-12|title=A genetic mutation panel for differentiating malignant phyllodes tumour from metaplastic breast carcinoma|url=https://pubmed.ncbi.nlm.nih.gov/29066183|journal=Pathology|volume=49|issue=7|pages=786–789|doi=10.1016/j.pathol.2017.07.011|issn=1465-3931|pmid=29066183}}</ref> and correlated with recurrence<ref name=":4" />
|-
|''TERT''
|promoter mutation
|Oncogene
|Common
|
|
|
|
|No significant difference between benign, borderline, and malignant tumors. Frequently co-mutated with ''MED12''.<ref name=":4" /><ref name=":6" />
|-
|-
|KMT2D (synonym MLL2)
|''CDKN2A''
|
|Inactivating mutations
|
|Tumor suppressor gene
|
|Recurrent
|
|
|
|
|More common in malignant tumors.<ref name=":4" />
|-
|''EGFR''
<br />
|Exon 18-21 activating mutations
|Oncogene
|Recurrent
|T
|
|
|More common in malignant tumors<ref name=":4" /><ref name=":3" />
|-
|''KMT2D''
|Inactivating mutations
|Tumor Suppressor Gene
|Recurrent
|
|
|
|
|Inactivation results in aberrant transcription regulation via epigenetic changes. No significant difference between benign, borderline, and malignant tumors.<ref name=":4" />
|-
|-
|ZNF703
|''NF1''
|
|
|
|
|
|
|
|Tumor suppressor gene
|Recurrent
|
|
|
|
|More common in malignant tumors.<ref name=":4" /><ref name=":6" />
|-
|-
|SETD2
|''PIK3CA''
|
|
|
|
|
|
|
|Oncogene
|Recurrent
|
|
|
|
|More common in borderline and malignant tumors.<ref name=":4" /><ref name=":6" />
|-
|-
|FLNA
|''RB1''
|
|
|
|
|
|
|
|Tumor suppressor gene
|Recurrent
|
|
|
|
|More common in malignant tumors. Gene deletions also common.<ref name=":6" /><ref name=":4" />
|-
|-
|RB1
|''SETD2''
|
|
|
|
|
|
|
|Other
|Recurrent
|
|
|
|
|Frequently co-mutated with ''MED12''. No significant difference between benign, borderline, and malignant tumors.<ref name=":6" /><ref name=":4" />
|-
|-
|NF1
|''TP53''
|Inactivating mutations
|Tumor suppressor gene
|Recurrent
|
|
|
|
|
|More common in malignant tumors.<ref name=":4" /> Germline mutations have been associated with phyllodes tumors.<ref>{{Cite journal|last=Rosenberger|first=Laura H.|last2=Thomas|first2=Samantha M.|last3=Nimbkar|first3=Suniti N.|last4=Hieken|first4=Tina J.|last5=Ludwig|first5=Kandice K.|last6=Jacobs|first6=Lisa K.|last7=Miller|first7=Megan E.|last8=Gallagher|first8=Kristalyn K.|last9=Wong|first9=Jasmine|date=2020-10|title=Germline Genetic Mutations in a Multi-center Contemporary Cohort of 550 Phyllodes Tumors: An Opportunity for Expanded Multi-gene Panel Testing|url=https://pubmed.ncbi.nlm.nih.gov/32504368|journal=Annals of Surgical Oncology|volume=27|issue=10|pages=3633–3640|doi=10.1245/s10434-020-08480-z|issn=1534-4681|pmc=9945652|pmid=32504368}}</ref>
|
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
|
 
|
|
|
|}
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.


==Epigenomic Alterations==
==Epigenomic Alterations==


Put your text here


==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==


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{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
|EXAMPLE: MAPK signaling
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|EXAMPLE: Increased cell growth and proliferation
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|-
|-
|EXAMPLE: CDKN2A; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
|EXAMPLE: Cell cycle regulation
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|EXAMPLE: Unregulated cell division
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|-
|-
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
|EXAMPLE:  Histone modification, chromatin remodeling
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
|EXAMPLE:  Abnormal gene expression program
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
|-
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|}
|}
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
 
Next generation sequencing. Chromosomal microarray for CNV detection can be considered if NGS testing does not call CNVs. Detection of CNVs can help differentiate between fibroadenomas and phyllodes tumors. FISH for EGFR amplification can also be considered in the absence of chromosome microarray or appropriate NGS assays.
Put your text here
 
==Familial Forms==
==Familial Forms==
 
Patients with Li-Fraumeni syndrome (germline TP53 pathogenic mutations) are at increased risk of phyllodes tumor.
Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
 
==Additional Information==
==Additional Information==
Due to the rarity of phyllodes tumors, most genomic studies are limited in number, and studies including patient follow-up information are very rare. Thus, the true mutation rate for rare events may vary compared to the numbers presented. In addition, very few studies have evaluated the prognostic value of genomic abnormalities.
==Links==
https://www.pathologyoutlines.com/topic/breastphyllodesgeneral.html
==Notes==


Put your text here


==Links==
<nowiki>*</nowiki>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 [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.


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Prior Author(s):


<br />
==References==
==References==
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<br /><references />
 
<nowiki>*</nowiki>''Citation of this Page'': “Phyllodes tumour”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/BRST5:Phyllodes tumour</nowiki>.
'''EXAMPLE Book'''
[[Category:BRST5]]
 
[[Category:DISEASE]]
#Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, 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, p129-171.
[[Category:Diseases P]]
 
==Notes==
<nowiki>*</nowiki>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.
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