BRST5:Phyllodes tumour: Difference between revisions

[[BRST5:Table_of_Contents|Breast Tumours (WHO Classification, 5th ed.)]]

<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)*==

==WHO Classification of Disease==

|Book

|Breast Tumours (5th ed.)

|Family

|Fibroepithelial tumours and hamartomas of the breast: Introduction

|Type

|Phyllodes tumour

|Subtype(s)

|N/A

|}

 

 

|Not Recommended

|Cystosarcoma phyllodes

==Gene Rearrangements==

!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)

!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

|''EGFR''

|

|}

!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

!Established Clinical Significance Per Guidelines - Yes or No (Source)

!Clinical Relevance Details/Other Notes

|

|

|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>

|Amp

|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>

|

|

|Observed in 39-57% of malignant tumors, 7-13% of borderline tumors; not observed in benign tumors<ref name=":1" />

|

|

|Significantly more common in malignant vs. borderline tumors<ref name=":0" /><ref name=":1" />

|Loss

|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>

|Loss

|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" />

|Loss

!Molecular Pathogenesis

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

|

!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

|''FLNA''

|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" />

|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''

|Common

|No significant difference between benign, borderline, and malignant tumors. Frequently co-mutated with ''MED12''.<ref name=":4" /><ref name=":6" />

|''CDKN2A''

|Recurrent

|

|

|More common in malignant tumors.<ref name=":4" />

|''EGFR''

 

|Recurrent

|More common in malignant tumors<ref name=":4" /><ref name=":3" />

|-

|''KMT2D''

|Inactivating mutations

|Recurrent

|

|

|Inactivation results in aberrant transcription regulation via epigenetic changes. No significant difference between benign, borderline, and malignant tumors.<ref name=":4" />

|Recurrent

|Recurrent

|

|Recurrent

|Recurrent

|

|

|Frequently co-mutated with ''MED12''. No significant difference between benign, borderline, and malignant tumors.<ref name=":6" /><ref name=":4" />

|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.

 

 

Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>

|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations

|<span class="blue-text">EXAMPLE:</span> MAPK signaling

|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation

|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations

|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation

|<span class="blue-text">EXAMPLE:</span> Unregulated cell division

|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations

|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling

|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program

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.

Patients with Li-Fraumeni syndrome (germline TP53 pathogenic mutations) are at increased risk of phyllodes tumor.

Prior Author(s):

<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>.