Origins of lymphatic and distant metastases in human colorectal cancer

Kamila Naxerova; Johannes G Reiter; Elena Brachtel; Jochen K Lennerz; Marc van de Wetering; Andrew Rowan; Tianxi Cai; Hans Clevers; Charles Swanton; Martin A Nowak; Stephen J Elledge; Rakesh K Jain

doi:10.1126/science.aai8515

Origins of lymphatic and distant metastases in human colorectal cancer

Kamila Naxerova, Johannes G Reiter, Elena Brachtel, Jochen K Lennerz, Marc van de Wetering, Andrew Rowan, Tianxi Cai, Hans Clevers, Charles Swanton, Martin A Nowak, Stephen J Elledge, Rakesh K Jain

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

346 Citations (Scopus)

Abstract

The spread of cancer cells from primary tumors to regional lymph nodes is often associated with reduced survival. One prevailing model to explain this association posits that fatal, distant metastases are seeded by lymph node metastases. This view provides a mechanistic basis for the TNM staging system and is the rationale for surgical resection of tumor-draining lymph nodes. Here we examine the evolutionary relationship between primary tumor, lymph node, and distant metastases in human colorectal cancer. Studying 213 archival biopsy samples from 17 patients, we used somatic variants in hypermutable DNA regions to reconstruct high-confidence phylogenetic trees. We found that in 65% of cases, lymphatic and distant metastases arose from independent subclones in the primary tumor, whereas in 35% of cases they shared common subclonal origin. Therefore, two different lineage relationships between lymphatic and distant metastases exist in colorectal cancer.

Original language	English
Pages (from-to)	55-60
Number of pages	6
Journal	Science
Volume	357
Issue number	6346
DOIs	https://doi.org/10.1126/science.aai8515
Publication status	Published - 07 Jul 2017

Keywords

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

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10.1126/science.aai8515

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@article{8be067193d8a4660bdaecc6c532b2ef1,

title = "Origins of lymphatic and distant metastases in human colorectal cancer",

abstract = "The spread of cancer cells from primary tumors to regional lymph nodes is often associated with reduced survival. One prevailing model to explain this association posits that fatal, distant metastases are seeded by lymph node metastases. This view provides a mechanistic basis for the TNM staging system and is the rationale for surgical resection of tumor-draining lymph nodes. Here we examine the evolutionary relationship between primary tumor, lymph node, and distant metastases in human colorectal cancer. Studying 213 archival biopsy samples from 17 patients, we used somatic variants in hypermutable DNA regions to reconstruct high-confidence phylogenetic trees. We found that in 65% of cases, lymphatic and distant metastases arose from independent subclones in the primary tumor, whereas in 35% of cases they shared common subclonal origin. Therefore, two different lineage relationships between lymphatic and distant metastases exist in colorectal cancer.",

keywords = "Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.",

author = "Kamila Naxerova and Reiter, {Johannes G} and Elena Brachtel and Lennerz, {Jochen K} and {van de Wetering}, Marc and Andrew Rowan and Tianxi Cai and Hans Clevers and Charles Swanton and Nowak, {Martin A} and Elledge, {Stephen J} and Jain, {Rakesh K}",

note = "Copyright {\textcopyright} 2017, American Association for the Advancement of Science.",

year = "2017",

month = jul,

day = "7",

doi = "10.1126/science.aai8515",

language = "English",

volume = "357",

pages = "55--60",

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TY - JOUR

T1 - Origins of lymphatic and distant metastases in human colorectal cancer

AU - Naxerova, Kamila

AU - Reiter, Johannes G

AU - Brachtel, Elena

AU - Lennerz, Jochen K

AU - van de Wetering, Marc

AU - Rowan, Andrew

AU - Cai, Tianxi

AU - Clevers, Hans

AU - Swanton, Charles

AU - Nowak, Martin A

AU - Elledge, Stephen J

AU - Jain, Rakesh K

PY - 2017/7/7

Y1 - 2017/7/7

N2 - The spread of cancer cells from primary tumors to regional lymph nodes is often associated with reduced survival. One prevailing model to explain this association posits that fatal, distant metastases are seeded by lymph node metastases. This view provides a mechanistic basis for the TNM staging system and is the rationale for surgical resection of tumor-draining lymph nodes. Here we examine the evolutionary relationship between primary tumor, lymph node, and distant metastases in human colorectal cancer. Studying 213 archival biopsy samples from 17 patients, we used somatic variants in hypermutable DNA regions to reconstruct high-confidence phylogenetic trees. We found that in 65% of cases, lymphatic and distant metastases arose from independent subclones in the primary tumor, whereas in 35% of cases they shared common subclonal origin. Therefore, two different lineage relationships between lymphatic and distant metastases exist in colorectal cancer.

AB - The spread of cancer cells from primary tumors to regional lymph nodes is often associated with reduced survival. One prevailing model to explain this association posits that fatal, distant metastases are seeded by lymph node metastases. This view provides a mechanistic basis for the TNM staging system and is the rationale for surgical resection of tumor-draining lymph nodes. Here we examine the evolutionary relationship between primary tumor, lymph node, and distant metastases in human colorectal cancer. Studying 213 archival biopsy samples from 17 patients, we used somatic variants in hypermutable DNA regions to reconstruct high-confidence phylogenetic trees. We found that in 65% of cases, lymphatic and distant metastases arose from independent subclones in the primary tumor, whereas in 35% of cases they shared common subclonal origin. Therefore, two different lineage relationships between lymphatic and distant metastases exist in colorectal cancer.

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, N.I.H., Extramural

KW - Research Support, U.S. Gov't, Non-P.H.S.

U2 - 10.1126/science.aai8515

DO - 10.1126/science.aai8515

M3 - Article

C2 - 28684519

SN - 0036-8075

VL - 357

SP - 55

EP - 60

JO - Science

JF - Science

IS - 6346

ER -

Origins of lymphatic and distant metastases in human colorectal cancer

Abstract

Keywords

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